Malignant Melanoma Healed with Natural Therapies

How To Prevent Skin Cancer

How To Prevent Skin Cancer

Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.

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How I Survived Malignant Melanom

By The Time You've Finished Reading How I Survived Melanoma Skin Cancer Seven Survivors Tell Their Stories. You'll Feel Like A New Person, with A New, More Positive Outlook! You will learn: 1. How do I know if I have melanoma? What are the signs and symptoms? I wanted to know why the doctor was so concerned when she looked at that little mole on my forearm. What was it that looked so sinister? How worried should I be? Was the doctor over-reacting? 2. What tests will the doctor carry out to see if I have melanoma? Will they be able to tell me on the spot if there is a problem? Or will I have to wait for days, fretting about whats going on? 3. How curable is melanoma? If they do tell me its melanoma, what exactly does that mean? Is it a death sentence? Will they tell me You have 12 months to live. Get your life in order and prepare for the worst.? 4. What are the stages of the disease? The reading Id done said that there were different stages of melanoma. What are the symptoms of each stage? What are the survival rates of each stage? If I had a later stage melanoma, wouldnt I know about it? Wouldnt I actually feel like I was sick? 5. How quickly does the disease progress or spread? Should I have gone to the doctor sooner? Id noticed the mole changing over about 3 months. Was this delay critical? 6. How is melanoma normally treated? Would I have to go through chemotherapy and radiation treatment? If so, for how long? What are the odds of curing the disease using these treatments? How extensive is any surgery likely to be? How big will the scars be? 7. What are the common side effects of the treatments? Would I lose my hair? Would I become sterile? What else could I expect? 8. What alternative treatments are available? Id heard of people going on special macro-biotic diets. Id seen lots of herbal remedies on the internet. Which of these are proven and documented, and which ones are snake oil? Is it possible to combine alternative treatments with surgical other western treatments? How do I find a doctor that is open to using both alternative and western treatments? 9. What are the latest treatments being developed, and who is carrying out clinical trials of these new treatments?

How I Survived Malignant Melanom Overview

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Mouse Model Of Subcutaneous Melanoma

The subcutaneous model is widely used for the evaluation of therapy in many tumor models, including B16 melanoma. Upon subcutaneous injection, B16 will form a palpable tumor in 5 to 10 days and grow to a 1 x 1 x 1-cm tumor in 14 to 21 days. When allowed to grow larger, the tumors often become necrotic in the center and begin to ulcerate or bleed it is advisable to sacrifice the mice before this point. The typical dose used is 1 x 105 cells mouse, which is 1.5 to 2 times the minimal tumorigenic dose in normal C57BL 6 mice. It is important to note that, for subcutaneous tumor growth experiments, a consistent injection technique is extremely important. Each mouse should show a clearly visible, defined bleb upon injection if not, a new mouse should be used. Mice without a clear bleb will show delayed tumor growth or no growth at all.

Classification of Melanoma

Clark et al. (1) defined four major histogenetic types of melanoma based largely on the growth pattern of their intraepithelial portions. These include superficial spreading melanoma (SSM), nodular melanoma (NM), lentigo maligna melanoma (LMM), and acral lentiginous melanoma (ALM). This classification has been challenged on the grounds that these types of melanoma have a similar prognosis when matched for sex, thickness, and site and that many of the characteristics of each type are, in fact, secondary to the site of the neoplasm or caused by secondary changes such as solar elastosis (2). Although there is general agreement that the Clark classification has neither independent prognostic value nor diagnostic relevance, the Clark nomenclature continues to be widely used in clinical practice. It also is entrenched in the medical literature regarding melanoma and correlates with the epidemiology of the disease. The histopathologic presentations of the four major histogenetic types of...

Clinical Evolution of Melanoma

Malignant melanomas may arise de novo, that is, in apparently normal skin or in association with a pre-existing melanocytic nevus. When malignant melanomas arise de novo, they begin as a small, lightly pigmented macule that in time is characterized by asymmetry, scalloped borders, poor circumscription, and variations in color of predominantly tan to brown (Fig. 1A). Some such macular lesions become patches that are increasingly asymmetrical, poorly circumscribed, and varied in color (Fig. 1B). Other macular lesions of melanoma eventually become papular or nodular. Some other macular lesions may simply enlarge to become patches, others plaques, and still others combinations of papules or nodules upon patches or plaques (Figs. 2A-C 3A and B). Some nodules and tumors ulcerate. Some melanomas may undergo partial or complete regression (Fig. 4). The clinical features of malignant melanomas just described apply to malignant melanomas at all anatomic sites of the skin and mucous membranes....

Histologic Evolution of Melanoma

A number of histologic features are common to melanoma in most locations and correspond to its evolution. The earliest lesions of most melanomas in situ, small macules clinically, appear microscopically as proliferations of solitary melano-cytes at or slightly above the dermal-epidermal junction spaced at irregular intervals (Fig. 6). The nuclei of the mela-nocytes in these early neoplasms may or may not be cyto-logically atypical but are almost always larger than those of the non-neoplastic basal melanocytes. As lesions of the melanoma in situ evolve, melanocytes can aggregate to form nests and spread to the upper spinous, granular, and cornified layers. Poor circumscription is a characteristic feature (Fig. 7). Often single neoplastic melanocytes will be visible beyond the last nest on either side of the lesion, and some of these cells may be situated above the basal layer. Melanoma in situ typically involves follicular infundibula with melanocytes distributed in the same pattern as...

Metastatic Melanoma Clinical Presentation

Local metastases of malignant melanoma include microsatellites, macrosatellites, and in-transit lesions. The macrosatellites and in-transit lesions present clinically as papules close to the primary melanoma (macrosatellites) or between the regional lymph nodes (intransit metastases) (Fig. 30). They usually are black or bluish in color, but sometimes are amelanotic, particularly if they are situated in the subcutaneous fat.

Nevoid Melanoma Definition

The term nevoid melanoma has been used to describe papular, predominantly intradermal proliferations of deceptively banal-appearing atypical melanocytes that are small and fairly symmetric thus resembling the architecture of a benign nevus. The concept is in evolution and is not universally accepted. Nevoid melanomas are rare and often are diagnosed retrospectively after metastases have occurred. It is likely that many so-called nevoid melanomas represent early NMs (6). Others are made up of large epithelioid mel-anocytes that resemble the cells of a Spitz's nevus. Since only a minority of such lesions actually behave in a malignant fashion, it is likely that many such lesions actually are Spitz's nevi that have been misdiagnosed.

B16 as a Mouse Model for Human Melanoma

Malignant melanoma is the sixth most common cancer in the U.S., with an estimated 44,200 new cases reported in 1999 (Centers for Disease Control and Prevention, 1999). A subset of patients with metastatic melanoma can be successfully treated by the administration of recombinant interleukin-2 (rIL-2), sometimes given together with autologous melanoma-reactive lymphocytes that have been expanded ex vivo (Rosenberg, 1997 Rosenberg, 1999). Recently, a number of different laboratories have used these anti-tumor lymphocytes to clone melanoma-associated antigens, which have generally been nonmutated melanocyte differentiation antigens (MDA), a group that includes MART-1 Melan-A, gp100, tyrosinase, and tyrosinase related proteins (TRP)-1 and -2 (Rosenberg, 1997 Rosenberg, 1999), and others listed in Table 20.1.1. With the possible exception of MART-1 Melan-A, each member of this group of proteins is an enzyme directly involved in the synthesis of eumelanin pigment (Winder et al., 1994...

Malignant Melanoma [87203 Fig 238

Gunshot Stippling

It is extremely rare for the cervix to be the primary tumor site for malignant melanoma (Fig. 238). Only a few cases have been reported in the literature (Hall et al. 1980) and recently summarized (Holmquist and Torres 1988 Cantuaria et al. 1999). Histogenetically, the tumor is of melanocytic origin. Occasional melanocytes can be found in the normal ectocervical epithelium (Stegner 1959). As in the skin, or elsewhere, the tumor is composed of pleomorphic round to spindle-shaped cells containing varying amounts of Fig. 238. Malignant melanoma. H& E Fig. 238. Malignant melanoma. H& E fine melanin pigment (Fig. 238). The tumor cells spread diffusely throughout the cervix, while the covering ectocervical epithelium usually remains intact. When melanin pigment is absent or very scanty, it is possible to distinguish the melanoma from undiffer-entiated carcinomas or sarcomas with the S-100 reaction, which is consistently positive in malignant melanoma.

Mouse Model Of Multiple Pulmonary Melanoma Metastases

The pulmonary metastasis model is the other widely used model for the evaluation of therapy in many tumor models, including B16 melanoma. Since essentially all tumor cells that take upon intravenous tumor injection are found in the lungs, the term pulmonary metastasis is widely used even though every resulting pulmonary nodule is technically an independent primary tumor rather than a true metastasis. The typical dose used is 2 x 105 cells mouse, which will yield between 50 and 250 pulmonary nodules visible on the lung surface. Since the melanin in B16 does not bleach like the rest of the pulmonary tissues, the tumor nodules can be easily visualized after bleaching of the extracted lungs in Fekete's solution (see Reagents and Solutions). There is always a fraction of nodules that is amelanotic (white) this requires careful counting in order not to underestimate tumor burden.

Melanoma Skin Cancer

M elanoma skin cancer is a type of skin cancer that originates from the melanocytes, frequently a nevus or mole. Melanocytes are melanin-producing cells that are interspersed in the inner layer of the epidermis. Melanin is a dark brown pigment that protects the epidermis and the superficial vasculature of the dermis. Nevi or moles are small, circumscribed aggregates of melanocytes. It is thought that the ultraviolet radiation (from direct sunlight or tanning beds) damages the DNA of melanocytes, impairing the DNA control over how and when cells grow and divide. These skin lesions tend to be hereditary, begin to grow in childhood, and become more numerous in young adulthood. Skin cancer is the most common cancer in the United States, and melanoma accounts for 4 of all skin cancer cases. Although the lifetime melanoma risk for the overall population is only 1.4 , melanoma is responsible for 79 of skin cancer deaths. According to the American Cancer Society, approximately 59,580 new...

Malignant Melanoma

Kaposi Sarcoma Flat Lesion

INTRODUCTION Cutaneous malignant melanoma is an invasive proliferation of malignant melanocytes, and accounts for 1 of all eyelid malignancies. The incidence increases with age, but remains relatively stable from the fifth to the seventh decades. Cutaneous malignant melanoma may be classified into four different types lentigo maligna melanoma (5 ), superficial spreading melanoma (70 ), nodular melanoma (16 ), and acral lentiginous melanoma (9 ). Nodular melanoma and lentigo maligna melanomas are the most common types affecting the eyelids. In all types, initially, a noninvasive horizontal growth phase occurs, which is followed by an invasive vertical growth phase. Changes in outline and color are features that tend to distinguish melanoma from benign pigmented lesions. Risk factors for the development of malignant melanoma include congenital and dysplastic nevi, changing cutaneous moles, excessive sun exposure and sun sensitivity, family history, age greater than 20 years, and...

Metastatic Melanoma

Melanocytic neoplasms constitute a spectrum of benign and malignant skin tumors that have distinct clinical, morphological, and molecular genetic profiles. Melanomas are neoplasms of melanocytes that have the potential to metastasize or are on an evolutionary pathway in which the acquisition of that potential is likely. Melanomas may develop within a pre-existing benign melanocytic nevus, but the great majority develop de novo. Intermittent high dose UV radiation is the major environmental risk factor for melanoma, but genetic factors undoubtedly play an important role. Melanomas are the most important group of cutaneous malignancies because of their inherent capability for metastasis. The most commonly affected anatomic sites are the face in both sexes, the ear, head, neck, back, and shoulders in men, and the legs in women. Melanomas begin as macules that may progress to plaques and tumors. Most begin as faintly uniform brown macules with slightly irregular borders. Over time, they...

Skin Cancer

Skin cancer is the most commonly occurring type of cancer in the United States. Experts estimate that 40 to 50 percent of Americans who live to age 65 will eventually develop some form of skin cancer. The risk is highest for people who have red or blond hair, light-colored eyes, and fair skin that freckles easily. The two most common forms of skin cancer are basal cell carcinoma, which accounts for more than 90 percent of all skin cancers, and squamous cell carcinoma. Basal cell carcinoma is a slow-growing cancer, found in the base of the outer layer of skin, that rarely spreads to other parts of the body. Squamous cell carcinoma, which affects cells in the surface of the skin, also spreads infrequently, although it does so much more often than basal cell carcinoma. A less common type of skin cancer, malignant melanoma, is the most serious form of skin cancer. It spreads quickly and can be fatal. The number of people with melanoma has more than doubled in the United States since about...

Is Sentinel Node Biopsy a Substitute for Elective Neck Dissection

Another controversy surrounding elective neck dissection concerns the value of sentinel node biopsy. Considering the experience with this technique in patients with melanoma and breast cancer, it is anticipated that gamma probe-directed biopsy of the sentinel node may be useful in the management of the NO neck in patients with squamous cell carcinoma of the head and neck. To that end, a recent study of 5 patients conducted by Koch et al.12 showed that identification and biopsy of the sentinel node are feasible in these patients. However, a number of substantial problems were identified (1) the proximity of the primary tumor obscures the lymphoscintigram, particularly when the tumor is located in the oral cavity (2) intramucosal injection of the radiolabeled material is more difficult than intradermal injections and the isotope often extrudes into the saliva and (3) some sites in the head and neck are inaccessible, and the technique is limited in patients who have been previously...

Drosophila melanogaster

The zebrafish system has proven useful for the identification of novel drug targets by the application of classical forward genetics (or knockdown by morpholino) to identify mutations that mimic human disease phenotypes. The obvious advantage of zebrafish over other model systems is that organ-level and vertebrate-specific diseases can be modeled. The first demonstration of the utility of zebrafish for identification of human disease genes was in the area of anemia the iron transporter ferroportin 1 was originally discovered in zebrafish116 and subsequently found to be mutated in the hereditary iron overload disease hemochromatosis.117,118 Models for polycystic kidney disease,119-121 melanoma,122 and various leukemias123-125 have been developed. Complex nervous system and sensory defects have been modeled in zebrafish, including neurodegeneration caused by heterologous expression of mutant tau126 and various forms of blindness and deafness.127,128

Occupational Exposure

The influence of occupational exposures was suggested by the excessive MF mortality rates in countries where petroleum, rubber, primary and fabricated metal, machinery, and printing industries were located (42,48). In a more recent study, employment in a manufacturing occupation (especially petrochemical, textile, metal, and machinery industries) was shown to be a risk factor (38). Workers employed in the petroleum industry have limited evidence for excess leukemia and other lymphatic and hematopoietic neoplasms, and skin cancer (particularly malignant melanoma) (49). Furthermore, studies on exposure to benzene in a multinational cohort of more than 308,000 petroleum workers followed from 1937 to 1996 indicated that these workers were not at an increased risk of NHL (50).

UVInduced Local Immunosuppression

UVB susceptibility and UVB resistance are not limited to mice but can also be found to a certain degree in humans (Yoshikawa et al. 1990). In addition, an association between the immunosuppressive effects of UVB and the development of skin cancer is evidenced by the significantly higher incidence of skin cancer in photosen

Evaluation of Eyelid Lesions

Telangiectasia Tympanic Membrane

From several recent large series looking at the frequency of eyelid lesions benign processes account for approximately 70 to 75 of all lesions, and malignant neoplasms for 25 to 30 (1-5). Among the benign lesions the most frequent diagnoses are squamous papilloma (26 ), nevus (22 ), cysts (20 ), seborrheic keratosis (13 ), vascular lesions (9 ), and neural lesions (< 1 ). The most common malignant tumor on the eyelid is the basal cell carcinoma followed in rapidly descending order by squamous cell carcinoma, sebaceous cell carcinoma, and malignant melanoma. Other rare tumors such as Kaposi's sarcoma, adnexal carcinomas, and Merkel cell tumor are occasionally seen, as are metastatic cancers. One large series of nearly 1100 malignant eyelid tumors from China showed the frequencies of basal cell and sebaceous cell carcinomas to be nearly equal at 38 and 32 , respectively, quite different from the usually quoted values from the Western literature. However, most other studies give the...

FSee 708 Kinase Inhibitors for Cancer

A deeper understanding of the molecular events leading to tumor formation, invasion, angiogenesis, and metastasis has provided a new mechanistic basis for oncology drug discovery targeted anticancer therapy.79 The rationale behind this approach is relatively simple specific inhibitors of proteins involved in aberrant signaling mechanisms would interfere with cancer progression, altering the natural course of the disease while sparing normal tissues. Although numerous disappointments have been harvested, we start to see how a new generation of targeted cancer agents - both low-molecular-mass inhibitors (e.g., imatinib, gefitinib, erlotinib)80 and humanized monoclonal antibodies (e.g., trastuzumab, cetuximab, becacizumab)77'81'82 - can provide incremental improvements over existing drug treatments. In addition to the identification of more effective anticancer agents, other areas under development include gene therapy (administration of tumor suppressor genes), immunotherapy (to boost...

Integrins and Downstream Signaling Pathways

Multiple signaling components are activated by FAK and SFKs including ETK, an intracellular tyrosine kinase found at high levels in metastatic carcinoma cells and the ERK MAPK and JUN kinase cascades, which, in addition to modifying gene expression, can affect motility by direct phosphorylation of cytoskeletal components.166 Activated SFKs phosphorylate and initiate signaling from paxillin and p130CAS.165 Modulation of motility and the actin cytoskeleton occurs principally via the consequent activation of the Rho GTPase family members Rho, Rac, and cdc42. Both Rac and Cdc42 are required for carcinoma motility and invasion, promoting actin polymerization at the leading edge of migrating cells.167 RhoA and RhoC are upregulated in metastatic carcinomas, and RhoC overexpression favors colonization of the lung in an experimental melanoma metastasis model. Rho, acting via two effectors, ROCK and mDIA, regulates actomyosin fiber assembly and contraction, contributing toward pulling forward...

Manufacture and Composition

Alteplase is synthesized using the cDNA for native human tPA derived from a human melanoma cell line. The cDNA is cloned into a Chinese ovary cell (CHO) cell line, from which suitable master and working cell banks are produced. Product manufacture entails culture of the producer animal cell line in a nutrient medium containing the antibiotic gentamicin. The glycosylated protein is secreted by the producer cell line into the extracellular culture medium. While production protocols remain confidential, initial product recovery is likely to involve physical removal of the producer cells from the product-containing culture media by means of filtration or centrifugation. This is likely to be followed by initial product concentration via ultrafiltration. Product purification entails application of multiple high-resolution chromatographic purification steps, including anion-exchange, gel filtration, and lysine-affinity chromatography. The final product has been shown to be > 99 pure by...

Tumor Necrosis Family Apoptosis and Immune Surveillance

KiSS-1 encodes a neuropeptide ligand for a GPCR hGPR54(AXOR12), identified as a gatekeeper of the reproductive cascade.223 KiSS-1 and hGPR54 display complementary expression patterns in the brain and in the placenta where they have been identified as regulators of trophoblast invasion, inducing migration and protease expression.224 KiSS-1 appears to play a similar role in tumor invasion and metastasis. Forced expression of KiSS-1 suppresses metastasis of melanomas and human breast carcinomas without affecting tumorigenicity.225-227 Although the action of Kiss-1 may depend on tumor type, loss of KiSS-1 expression was correlated with tumor recurrence in gastric cancer and venous invasion and distant metastasis in invasive bladder cancer patients. Additionally, loss of KiSS-1 and or hGPR54 gene expression was found to be a significant predictor of lymph node metastasis in esophageal squamous cell carcinoma (ESCC).217 Upon entering the vasculature, mechanical forces contribute to the...

Types Of Microarray Experiments

A third set of experiments is described as class discovery. In contrast to the two classes described previously, class discovery discerns between individual members of an otherwise homogenous group of tissue sample solely based on their expression profile. The objective is to define subsets, or clusters, of the cases based on differences of gene expression. This approach has been successfully used to subclassify advanced melanoma where no clinical classification existed (5). Subsequently, this

Fibroblast Growth Factor and Angiogenesis

Multiple studies have documented expression of FGF ligands, particularly FGF2, within tumors. Abrogation of FGF signaling has been shown to inhibit neovascularization and growth of experimental tumors, while a synergistic effect on tumor vessel density is observed upon administration of VEGF-A and FGF.266,267 However, whereas a consistent correlation between tumor microvessel density and VEGF-A expression has been documented, there appears to be marked heterogeneity when FGF levels are examined. One notable exception is melanoma, in which FGF2 levels and microvessel density are clearly correlated.268

Comparative trial See controlled trial

Example In the 1980s, a study found a strong association between use of oral contraceptives and risk of malignant melanoma. It subsequently became evident that the women who used oral contraceptives, being younger, exposed themselves to the sun more often than non-users. Adjustment for duration of sun exposure substantially decreased the value of the odds ratio quantifying the strength of the association between oral contraceptives and malignant melanoma. Sun exposure, linked both to the probability of oral contraceptive use and the occurrence of malignant melanoma, acted as a confounder in this study.

Platelet Derived Growth Factor

Whereas VEGF-A is predominantly required during the initial steps of angiogenesis (formation of the endothelial plexus) subsequent steps, involving recruitment and vessel coverage by pericytes and smooth muscle cells, appear to be dependent on other soluble factors, e.g., PDGF PDGF-B acts as a pericyte and smooth muscle cell chemoattractant whereas TGF-b has been implicated in vessel stabilization.269,270 Microscopic examination indicates that tumor capillaries possess mural cells however, unlike normal vessels in which pericytes are well organized and closely associated with the endothelial compartment, tumor pericytes were present at a lower density and appeared more loosely attached.271 Positive immunohistochemical staining for PDGFR-B, originating from associated pericytes, was observed in tumors.194 Experimental manipulation of PDGF levels has demonstrated that release of PDGF from both endothelial and tumor cells can impinge on pericyte recruitment to tumor vessels.272...

Deregulated Cytosolic Signaling Pathways

Different growth factors and cytokines transduce their growth-promoting signals through the activation of the small G protein Ras (Figure 4). This leads to activation of members of the Raf family of serine threonine kinases (c-Raf, A-Raf, and B-Raf) and its downstream effector, the mitogen-activated protein kinase (MAPK) kinase (MEK). This protein then phosphorylates and activates MAPK, the so-called extracellular signal-regulated kinase (ERK). The Ras-Raf-MEK-MAPK pathway controls the growth and survival of a broad spectrum of cancers. Thus, it has been shown by the expression of dominant negative or activated forms of MEK that the expression of cyclin D1, which leads to transition from G1 to S phase, is controlled by MEK signaling.287 Activating mutations in Ras and Raf are present in a large percentage of solid tumors. For example, the Ras oncogene is found mutated in its oncogenic form in 15 of human cancers, with subsequent activation of the MAPK pathway.288 The MEK and ERK...

Differential Diagnosis

Gically from MF by the presence of marked hyperkeratosis, prominent pagetoid epidermotropism of somewhat larger cerebriform cells and paucicellular dermal infiltrate lacking eosinophils (11,17). Histologically, superficial spreading melanoma and Paget disease may mimic PR, but can readily be distinguished by cytomorphologic and immunophenotypic features (S-100 CEA EMA) (18,19).

Gastrointestinal Stromal Tumors GISTs

Magnetic Resonance Metastatic Intestinum

A CT scan may add considerably to the pre-operative evaluation of these tumors. CT can accurately demonstrate the size, shape and extent of the lesion, uniformity of densities and enhancing patterns, and it can depict the presence of liver, peritoneal or other metastases. CT is useful in the differentiation from other malignant tumors that often have a predominantly submucosal location and or appear largely excavated, such as lymphoma or metastatic melanoma. The main differential diagnosis of malignant GISTs, however, includes their benign counterparts, benign smooth muscle or neurogenic tumors. CT criteria favoring malignancy include an irregular, lobu-lated, large-sized mass, heterogeneous tissue density, central liquefactive necrosis, seen as water density with or without air fluid level, ulceration or fistula formation. Liver metastases from malignant GISTs are large, necrot-ic or cystic in nature with peripheral or 'rim' enhancement, whereas peritoneal metastases may appear as...

Antibodies Induced By Cytokine Therapy

IFN-P-neutralizing Ab were first demonstrated in high-risk malignant melanoma patients receiving combination therapies of recombinant IFN-P and IFN-Y (141). Although no Ab to IFN-y were found, 56 developed IFN-P-neutralizing Ab notably in patients receiving IFN-P subcutaneously. In 1993, IFN-P was shown to reduce the exacerbation frequency and decrease lesion formation visualized by magnetic resonance (MR) scans in patients with multiple sclerosis (MS) (142). On this basis, prolonged therapy with two recombinant IFN-P products has been approved for the treatment of MS a glycosylated form with the predicted natural amino acid sequence (IFN-P 1a) and a nonglycosylated form with a Met-1 deletion and a Cys-17 to Ser mutation (IFNP1b) (143).

Analysis of Cytotoxic Agents in Xenograft Models

The data include several examples of cytotoxic agents that show significant xenograft activity that is reflective of clinical activity irinotecan is highly active in several models of colon cancer, temozolomide is efficacious in a model of glioma and one of two models of melanoma, paclitaxel is active in models of bladder, breast, lung, and prostate cancer, rituximab is highly active in two models of B-cell lymphoma, and gemcitabine is active in a model of pancreatic cancer. Note, however, that this activity can be quite dependent on the dose and schedule employed (note irinotecan in colon cancer models). Correlating dose and schedule with PK (e.g., efficacy driven by Cmax, area under the curve (AUC), time over threshold, etc.) is a vital aspect of preclinical evaluation in order to help define the optimum clinical schedule (once- versus twice-daily administration, continuous versus intermittent therapy, etc.). Table 1 also highlights some of the differences in activity that can be...

Carcinogenicity Mutagenicity Studies

Robinson et al. 32 examined hyperplasia in mouse skin after dermal exposure to sodium hypochlorite, hypochlorous acid, and to the hypochlorite ion. The stated goal of this study was to examine the potential for these compounds to promote skin cancer. The study consisted of exposing the skin of SENCAR mice to concentrations of 0.001-0.1 of various chlorine compounds. All of these compounds resulted in some degree of hyperplasia. The author's decision to use the ability of sodium hypochlorite, and its derivatives, to induce hyperplasia (thickening of the skin) as an indicator of the substance's tumor promoting capacity was based upon the 'excellent correlation' between the hyperplasiogenic activity and tumor promotion among phorbol esters. However, the author admits that this correlation does not hold true for compounds of chemical classes other than phorbol esters. Given that the correlation between skin hyperplasia and tumor promotion appears to be limited to phorbol esters, and that...

Disclaimer Not for patient use To be used as a research guide only

PD markers have long been used in phase I studies to determine the optimal dose by assessing serum plasma levels of the drug in conjunction with safety and toxicology parameters. Other analytes in either blood or urine associated with disease can also be evaluated if the pathogenesis of disease is understood and it is in this context where discovery of novel biomarkers of disease may be greatly aided by genomic, proteomics and metabolomics.67,86 Functional biomark-ers, an extension of a pharmacodynamic type of biomarker, are biochemical measures that indicate the drug is reaching its target and affecting its proposed mechanism of action. Evaluating cell death in cancer therapies may soon be possible using an enzyme-linked immunosorbent assay (ELISA)-based assay measuring caspase 3-mediated apoptosis in solid tumors (Cyclacel, UK),75 but it will be limited to accessible tumor types. Recently, functional biomarker assays for PARP inhibition were demonstrated in metastatic melanoma from...

Predisposition to papillomaviruses epidermodysplasia verruciformis

Epidermodysplasia verruciformis (EV) is characterized by selective susceptibility to infections caused by skin-tropic oncogenic papillomaviruses (HPVs) of the B1 group, leading to an increase in the risk of epithelial skin cancer. It was first described clinically in 1922 (Jablonska & Majewski 1994). Autosomal recessive mutations in two adjacent genes, EVER1 and EVER2, were described in 2002 in three and two kindreds, respectively (Ramoz et al 2002). One patient with compound heterozygous mutations in EVER1 and another with a homozygous mutation in EVER2 were recently described (Tate et al 2004, Sun et al 2005). EVER genes belong to the transmembrane channel-like (TMC) family of genes, encoding proteins with eight membrane-spanning domains, thought to act as ion channels, transporters, or their associated modifiers (Kurima et al 2003, Keresztes et al 2003). The TMC family was first discovered by positional cloning of human

Meinhard Wlaschek and Karin Scharffetter Kochanek Introduction

There is a strong association between exposure to ultraviolet irradiation (UV) induced reactive oxygen species (ROS), human skin cancer, and premature aging of the skin.1-3 Reactive oxygen species (ROS) are part of normal regulatory circuits and the redox state is tightly controlled by antioxidants. Cells and tissues are equipped with a complex enzymatic and nonenzymatic antioxidant defense system.

Clinical Application Questions

A 70-year-old man is seen at your office for multiple raised pigmented lesions over his back and chest. These have developed gradually over several years. There are two lesions on the mid-lower back that intermittently itch intensely and are somewhat larger and much darker than the other lesions, which number 50 or more. Physical examination of the entire region reveals multiple seborrheic keratoses. Except for the two lesions in question there are no other suspect lesions. The patient is very worried about melanoma. 1. Should the two darker lesions be biopsied for melanoma

Microdistribution None

The vast majority of SKs can be diagnosed by physical inspection. Depending on their stage of evolution, there are times when SKs may be difficult to distinguish clinically from a pigmented basal cell carcinoma, lentigo maligna, or a malignant melanoma. In these rare instances the lesion should be referred to a dermatologist for evaluation and a decision regarding the appropriate type of biopsy if one is indicated. Malignant Melanoma and Pigmented Basal Cell Carcinoma

Evaluation of Patient

A careful history may elicit symptoms of pain in the oral cavity, the oropharynx, or hypopharyngeal areas, possibly with referred otalgia. Symptoms of hoarseness, dysphagia, odynophagia, or hemoptosis, or the awareness of a mass or ulcer in the oral cavity or the oropharynx, may alert the physician to the possible site of a primary tumor. One should inquire about symptoms such as weight loss, fever or night sweats, abdominal pain, melena, diarrhea, and hematuria. The patient should be questioned about history of thyroid or skin cancer or other tumors, including tumors below the clavicles (i.e., in the GI tract, lung, or GU tract). For example, renal cell carcinoma may metastasize to the head and neck 10 to 15 years or more after the initial diagnosis.

Histopathologic Diagnosis

The histopathologic type of metastatic cervical lymphadenopa-thy for which a primary cannot be identified is squamous cell carcinoma in about 80 of the cases.2 The remainder are adenocarcinomas, melanomas, undifferentiated carcinomas, and small cell carcinomas.6 The diagnosis can usually be reliably established in most cases with a fine-needle aspiration biopsy (FNAB), particularly with metastatic squamous cell carcinoma. Certain instances in which the aspiration biopsy is indeterminate or suggestive of lymphoma require an open cervical lymph node biopsy. The histopathology of the metastasis provides information that can aid in the search for a primary site and that is used for appropriate management decisions. Adenocarcinoma in low cervical lymph nodes only is strongly suggestive of an infraclavicular primary lesion. In such cases, further exhaustive evaluation of the upper aerodigestive tract is not warranted. The diagnostic evaluation would shift to focus on the organs being the...

Cadherins and epithelialmesenchymal transition EMT

Changes in expression of other cadherins accompanies downregulation of E-cadherin, in a situation reminiscent of the epithelial-mesenchymal transition that occurs during embryonic development. This transition is characterized by a loss of epithelial cell polarity and cell-cell contact, gain of mesenchymal markers such as N-cadherin, and an increased migratory phenotype.154 Increased levels of N-cadherin, normally expressed in neuronal cells and fibroblasts in adults, are observed in breast and prostate cancer and invasive melanoma.155 N-cadherin is thought to mediate a less stable and more dynamic form of cell-cell adhesion, and its overexpression enhances invasion and formation of metastasis. These changes occurred despite the presence of E-cadherin, suggesting that N-cadherin may play a dominant role. N-cadherin invasive activity occurs, at least partly, via association with the fibroblast growth factor receptor-1 (FGFR-1). Interaction results in stabilization of FGFR-1 leading to...

Genetic Considerations

While both sporadic and familial forms of this disorder seem to exist, family history has been associated with an earlier onset, less invasiveness, and smaller lesions. A pattern of autosomal dominant transmission is seen in some populations. A person with one first-degree relative affected by melanoma has 2 to 3 times the risk of the general population and 6 times the risk if the relative was affected before age 50. The risk increases 13-fold if more than one first-degree relative is affected.

Gender Ethnicracial And Life Span Considerations

Men have a 1 57 chance of developing melanoma women have a 1 81 chance. The incidence of melanoma increases with age 50 of cases occur in people who are older than age 50. Mortality rates are increasing most rapidly among European American men older than age 50. Although melanomas are rare in children, the incidence among today's younger people, however, is proportionally higher than among people of the same age decades ago. Melanoma is one of the most common cancers in people who are younger than age 30. European Americans have a 20 times higher risk factor for melanoma than do African Americans. Melanoma most often appears on the trunks of fair-skinned men and the lower legs of fair-skinned women however, people with more darkly pigmented skin do develop melanoma on their palms, and soles and under the nails.

Diagnostic Highlights

Presence of melanoma cells Presence of melanoma cells Removes a deep sample of skin melanoma cells after numbing the site cuts through all layers of skin Presence of melanoma cells Presence of melanoma cells Uses a thin needle to remove a very small tissue fragment may be used to biopsy a lymph node near a melanoma to determine the extent of the disease

Primary Nursing Diagnosis

After diagnostic testing, the cancer is staged. Because the thinner the melanoma, the better the prognosis, the Clark level of a melanoma may be used. This system uses a scale of 1 to 5 to describe which layers of skin are involved. The higher the number, the deeper the melanoma. The primary treatment for melanoma is surgical resection. Excision of the cancerous lesion with a 2- to 5-cm margin is recommended when feasible. The width of the surrounding margin should be wider for larger primary lesions. When the melanoma is on a finger or toe, surgical treatment is to amputate as much of the finger or toe as is necessary. Elective regional lymph node removal is controversial. Proponents believe that this procedure decreases the possibility of distal metastases, but scientific evidence to support this belief is lacking. The prognosis for metastatic melanoma is poor it is highly resistant to currently available chemotherapeutic agents. Radiation is not often used to treat the original...

Use of GFP to Study Cytoskeletal Filaments

Japanese Photos Moon Structures

Cytoskeletal systems visualized with GFP. GFP-tagged cytoskeletal proteins show actin dynamics in living melanoma cells (A used with permission from Andrew Matus), intermediate filaments in living BHK cells (B used with permission from Robert Goldman), and microtubule remodeling in living CHO cells (C used with permission from Beat Imhof). Fig. 1. Cytoskeletal systems visualized with GFP. GFP-tagged cytoskeletal proteins show actin dynamics in living melanoma cells (A used with permission from Andrew Matus), intermediate filaments in living BHK cells (B used with permission from Robert Goldman), and microtubule remodeling in living CHO cells (C used with permission from Beat Imhof).

Integrin Expression on Osteogenic Cells

Originally, MG-63, HOS and Saos-2 cells were derived from osteogenic tumors, more precisely, from osteosarcomas. However, they do not behave like malignant cells and grow in soft agar or generate tumors in nude mice. In cell culture they differentiate under appropriate conditions, but by treating HOS cells with a chemical mutagen, like N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), or exposing them to murine Kirsten sarcoma virus, tumorigenic derivatives of HOS cells are generated (in this case, named HOS-MNNG, and KHOS-NP). These cell lines show, in addition to a1p1 integrin, strongly enhanced of a2p1 integrin35 expression. Two nontumorigenic revertants of KHOS-NP, KHOS-240 and KHOS-312, have moderate expression of both a1p1 and a2p1 integrins.35,36 The link between a2p1 integrin expression and malignant cell phenotype in osteogenic cell lines also raises the question regarding the putative contribution done by a2p1 integrin to the cancer cell behavior. The fact that a2p1 integrin is...

Conditions That May Simulate Common Nevi

Small nodular basal cell carcinomas and small minimally pigmented dome-shaped compound or dermal nevi may be difficult to distinguish clinically. Helpful (but not absolute) signs are the translucency of the basal cell and the small dilated vessels that often course irregularly over its surface. A centrally located indentation or dell favors the basal cell carcinoma. In addition, there is an uncommon type of pigmented basal cell carcinoma that can sometimes simulate a pigmented nevus or melanoma. A derma-tologic consultant can usually tell on clinical exam or advise as to the appropriate approach. These common fibrous growths occur at frequent sites of blunt trauma such as the shins, shoulders, and upper back. They are usually 6 mm or less in size, and often develop a smudgy tan pigmentation over their surface. They can be distinguished clinically from true moles by their firm feel, like a button under the skin surface. Also they often show a positive pucker sign with lateral...

What should you tell the patient about the solar lentigines

Answer Widespread solar lentigines are the result of chronic sun exposure, and generally are not treated. The patient should be warned about a small increased lifetime risk of melanoma, and should be counseled regarding sun avoidance, protective clothing, and use of sunscreen. Monthly self-examination based on the ABCD (Asymmetry, irregular Borders, variegated Coloration, large Diameter) system should be advised along with yearly office follow-up and immediate follow-up for a changing lesion.

Vitronectin Receptor Integrins and MMP Expression

Cells bind to vitronectin through aV-integrins and when the small dermatan sulfate proteoglycan decorin is present with vitronectin, this binding is accompanied with induced MMP-1 expression.68 This induction was also observed when decorin was present with the exposed cell binding domain of fibronectin, but not when intact fibronectin was used. aVp3 heterodimer, is the most abignitions of all integrins and binds to vitronectin, fibronectin, fibrinogen, laminin, tenascin, denatured collagen, von Willebrand factor and osteopontin. It plays a significant role in angiogenesis, is expressed in both migratory and metastatic cells,40,41 and in addition to cell motility can regulate matrix degradation. In vivo, aVp3 is localized on the cell surface with MMP-2 in a functionally active form in vivo in angiogenic blood vessels and melanoma tumors.76 It can not bind to native collagen, but may interact with denatured collagen, and therefore could possibly regulate collagen degradation and the...

Antibody Induced MMP Expression

Many different studies demonstrate the variety of antibodies capable of triggering MMP-2 expression. In melanoma cells it is antibodies against a5p1 and aVp3 integrins,70 in glioma cells antibodies against a3p1 and a5p1,71 and in rhabdomyosarcoma cells anti-a2 and anti-a3 antibodies.72

Conditions That May Simulate Atypical Nevi

Persons with large numbers of solar lentigines or an abundance of common nevi over their upper torso may, on initial inspection, appear to have this syndrome. Solar lentigines are monotonous and show similar size and coloration. In addition, color tends to be constant throughout each individual lesion. Common nevi also tend to resemble one another in a given individual. They do not show the variable warning signs (ABCDs) of melanoma. Common nevi generally are 6 mm or less in size. Although the risk is not as high as in atypical nevus syndrome, there is evidence that the presence of large numbers of uniform, small, darkly pigmented nevi, the cheetah phenotype, is also a marker for increased melanoma risk.These moles individually resemble nonsolar lentigines, but the profusion of lesions is very striking.

Clinical manifestation

Congenital variant size ranging from < 1 cm to lesions covering most of the integument range in color from tan to deep blue-black may begin as patch and become palpable as child ages associated satellite pigmented papules, especially in patients with giant congenital nevus (> 20 cm in diameter) melanoma risk increases with size of congenital lesion Clark's nevus (atypical mole, dysplastic nevus) variant reddish-brown flat papule, with central elevation and feathered red border (fried egg appearance), often > 0.5 cm in diameter sometimes marker of risk for melanoma, particularly with family history of melanoma or presence of multiple lesions

Indicated Supporting Diagnostic Data

LCMN are clinically self-evident tissue examination is done only at the time of definitive excision or when changes within them suggest the possibility of malignancy. In addition to malignant melanoma, benign and malignant hamartomas and active nevus regression can produce symptomatic change in these lesions. A well-placed punch or small wedge biopsy may be indicated before a major procedure is undertaken. instances, cause hydrocephalus and seizures. In addition, melanoma can arise in the CNS portions of the mole. Magnetic resonance imaging (MRI) can delineate this involvement and explain these neurologic findings. Furthermore, when making a decision regarding removal of one of these lesions, the presence of CNS involvement may, for the family, be an important part of the decision process.

Hepatobiliary System of Pancreas

Tumors can develop in both the exocrine and the endocrine tissue of the pancreas, although 95 arise from the exocrine parenchyma (functional tissue) and are referred to as adenocarci-nomas. The remaining 5 of pancreatic tumors develop from endocrine cells of the pancreas they are named according to the hormone they produce (i.e., insulinomas, glucagonomas). Adenocarcinoma of the ductal origin is the most common exocrine cell type (75 to 92 ), and it occurs most frequently in the head of the pancreas. Pancreatic adenocarcinoma grows rapidly, spreading to the stomach, duodenum, gallbladder, liver, and intestine by direct extension and invasion of lymphatic and vascular systems. Further metastatic spread to the lung, peritoneum, and spleen can occur. Metastatic tumors from cancers in the lung, breast, thyroid, or kidney or skin melanoma have been found in the pancreas.

Dermatologic Physical Exam

Physical examination of pigmented lesions is a difficult task and is best approached by using the ABCD technique mentioned earlier in the chapter on atypical nevi (see Chapter 28). If a lesion is abnormal by these criteria, and especially if there is also a history of distinct change or evolution over the prior 6 to 12 months, there is a high probability of melanoma. Many benign moles will have one of these changes. A melanoma usually shows several or all. Asymmetry In Chapter 28, benign nevi are described as usually round or oval in shape. The disordered growth of melanoma cells tends to produce distinct variations in the symmetry of the lesion. This is particularly true with SSMM, LMM, and ALMM (see Photos 26-30,32). Border Benign moles usually have distinct, smooth, regular borders, which are easily marked. Melanoma margins are irregular, pseudopod-like, or grossly notched. This is typical of SSMM (see Photos 26,29,30,32,33). Indistinct margins that fade into the adjacent skin may...

Hydroxamate Inhibitors for Blocking Tumors

In animal models, batimastat has been reported to inhibit tumor growth and spread (modest effect in the latter) of B16-BL6 melanoma cells injected in mice,6,101 inhibit angio-genesis and reduce tumor doubling time in hemangiomas in mice by inhibiting recruitment and organization of vascular cells and structures,102 human breast cancer regrowth and metastasis in a nude mouse xenograft model,103 reduce human colon cancer growth and local, regional and distant spread as well as reduce ascites volume and improve survival in a mouse model,104-106 and in human ovarian cancer.107 However, the drug was ineffective in preventing colonization in multiple organs following intraperitoneal injection of a Burkitt lymphoma cell line into SCID mouse model, using PCR to detect the presence of the malignant clone.6 Recently, AG3340, a nonpolypeptide MMP inhibitor whose design was based on the crystallographic data accumulated so far, has shown picomolar K s against MMP-2, MMP-3, and MMP-9. In a Lewis...

Phosphorothioate Oligos

Therefore, it may be desirable to develop antisense inhibitors against each MMP target with the eventual goal of mixing and matching agents to a particular therapeutic goal. Antisense oligonucleotides targeted directly against MMP mRNAs have been reported now for several MMPs. Antisense methylphosphonate oligonucleotides have been used against MMP-2 or MMP-9 to selectively inhibit their activity in HT1080 fibrosarcoma cells.139 The MMP-2 antisense oligonucleotide was directed at the initiation codon while the MMP-9 antisense oligonucleotide targeted the upstream 5' untranslated region. Specificity for each target was maintained at concentrations from 5-50 iM, and was lost at 100 iM where growth inhibition was also observed after 120 hours of exposure the antisense agent. MIM human melanoma cells have been stably transfected with a plasmid vector expressing a 777 nucle-otide frangment complementary to MMP-1 mRNA.140 In two clones, MMP-1 mRNA expression was blocked 90-96 with...

The Clinically and Histologically Atypical Melanocytic Nevi The SoCalled Dysplastic Nevus

Benign melanocytic neoplasms constitute an increasingly important and diverse group of cutaneous lesions. Their importance is derived from their relationship to malignant melanoma as simulants, risk markers and precursors to melanoma. As such they pose a significant diagnostic challenge to both clinicians and pathologists because of their profound heterogeneity and capacity to mimic melanoma. There is also evidence that along with cutaneous melanoma melanocytic nevi are increasing in frequency worldwide. Both genetic and environmental factors clearly influence the development of melanocytic nevi. Increased numbers of nevi aggregate in some families, and the pheno-type of multiple nevi and or enlarged nevi is linked to melanoma-prone kindreds and, in fact, is the strongest epidemiological risk factor for melanoma. These familial associations indicate a genetic basis for the growth and development of nevi. Quantification of total nevus number and total nevus density in melanoma kindreds...

Classification and Criteria for Benign Melanocytic Neoplasms

In the routine evaluation of melanocytic lesions one is continually faced with the decision as to whether a lesion is benign or malignant. In approaching this problem one has to apply a number of criteria for this interpretation (Table 4) since no single criterion is sufficient. At present there is no universal consensus as to which criteria should be included in this exercise, or the relative importance or relative weight of each criterion. It is certain that this latter exercise should take into consideration clinical information, organizational, cytological, and cell proliferation-related properties of the individual lesion. It must be emphasized that there are exceptions to each criterion, and the failure to consider this may result in both over- and underdiagnosis of melanoma.

Table 1 Clinical Criteria Used for the Classification of Benign Melanocytic Neoplasms

Diagnosis a certain percentage of melanocytic lesions cannot be easily interpreted as benign or malignant. Consequently the author utilizes a third or intermediate category reserved for melanocytic lesions occupying the continuum between benign and malignant. An intermediate category avoids overdiagnosis of melanoma and also the under-recog-nition of abnormal or indeterminate lesions that require additional therapy and close monitoring, rather than being pronounced benign without further qualification. The criteria and nomenclature for (and some would argue even the very legitimacy of) such intermediate lesions are presently a source of considerable controversy and debate. The various terms suggested for such intermediate lesions have not as yet been standardized, as evidenced by nomenclature such as atypical nevi, dysplastic nevi, nevi with architectural disorder and cytological atypia, Spitz tumors with atypical features (atypical Spitz tumors), atypical cellular blue nevi, and so...

Halo Melanocytic Nevus

Halo nevi are common nevi exhibiting a peripheral vitiligo-like annulus or halo of hypopigmentation or depigmentation surrounding a central nevus (Fig. 4A). Histologically halo nevi demonstrate a dense lymphocytic infiltrate associated with the central nevus and a peripheral zone of hypo- to depigmentation of the epidermis, corresponding to the clinical halo (Fig. 4B). Halo melanocytic nevi may exhibit both clinically and histologically atypical features and thus raise concern for melanoma (Tables 4 and 7).

And Collagenaseresistant rr MICE

These findings illustrate aspects of the dynamic relationship in a specific tissue between collagen synthesis, on one hand, and collagen degradation on the other. We have noted, in unpublished observations, using riboprobes for the mouse interstitial collagenase and in situ hybridization, that there is expression of the collagenase mRNA of a spotty nature in clusters of basal keratinocytes in the skin (also see chapter 12). Some cells in the dermis, presumably fibroblasts, also show the presence of collagenase mRNA. Collagenase-1 (MMP-1) is also expressed in human keratinocytes in inflammation and wounding.43-45 Data from several laboratories indicate that epithelial cells such as keratinocytes as well as various mesenchymal cells bind to type I collagen matrices using a2p1 integrins on the cell surfaces46,47(see chapter 8). In wounded epidermis, migrating keratinocytes continue to express these collagen-binding a2p1 integrins but then redistribute them such that they are concentrated...

Caspases And Disease State

A relatively frequent event in malignant melanoma (Soengas et al., 2001). Gene ablation experiments in mice have established that ablation of any of the major caspase genes (caspase-3, -8, and -9) is lethal, suggesting that inherited mutation of these genes is an unlikely probability (Evan and Vousden, 2001) and such mutations must be acquired by tumor cells. Little is known about mutation of caspases leading to disease. The only example to date is a nonsense mutation of caspase-10 gene that is associated with the nonmalignant auto-immune lymphoproliferative syndrome ALPS type II (Van Der Werff Ten Bosch et al., 2001). The deletion of exon 3 of the caspase-3 gene in the MCF7 breast carcinoma cell line (Janicke et al., 1998) renders these cells more resistant to a variety of apoptotic stimuli, concomitant with the central role of this caspase in the execution phase of the cell death program. The next few years will undoubtedly reveal many as yet unknown pathological implications of...

Background Information

B16 melanoma is a spontaneous melanoma derived from C57BL 6 mice. As a model for human tumors, it is important to note similarities and differences between B16 and human melanomas (see Table 20.1.2). Several variants were isolated by Dr. Isaiah J. Fidler in the mid-1970s, the main differences between sublines being their metastatic potential and susceptibility to immune destruction (Fidler et al., 1976 Fidler and Bucana, 1977). The most commonly used variant is B16.F10, which is highly aggressive and will metastasize from a primary subcutaneous site to the lungs, as well B16 melanoma is one of the very few pig-mented melanoma lines available for use in mice, although recently transgenic models have been developed in which the reliable incidence of melanoma allows the establishment of new lines (Chin et al., 1997 Otsuka et al., 1998 Zhu et al., 1998). In addition, a recent report de- B16 as a Mouse Model for Human Melanoma

Regulation of Collagenase Inhibition The Role of TIMPs in Cancer

TIMPs are the primary inhibitors of collagenases, as well as all other MMPs.67 To date, there have been four human TIMPs identified (TIMPs 1-4), all with similar secondary structure but with somewhat different inhibitory capabilities against the various MMPs (Fig. 11.1). TIMPs bind MMP active sites, forming stoichiometric, noncovalent complexes. By doing so, TIMPs comprise the third part of the MMP regulatory triad, the other parts consisting of MMP expression and activation. The best evidence that MMPs play a critical role in tumor progression is the ability of TIMPs to block tumor progression. This was demonstrated by Schultz et al, who used recombinant TIMP-1 to block tumor invasion in vitro and in vivo.68 Similarly, Khokha et al used antisense cDNA constructs to block TIMP expression in mouse 3T3 cells, and found that decreased TIMP expression correlated with increased invasiveness in vitro and in vivo.69 TIMP levels in metastatic cells lines have repeatedly been shown to...

Spitz Tumor With Atypical Features

A subset of Spitz tumors may be difficult or impossible to distinguish from melanoma and may exhibit one or more atypical features such as large size (often > 10 mm), asymmetry, poor circumscription, ulceration, deep involvement, high cellular density, confluent or nodular grow patterns, diminished or absent maturation, cytological atypia beyond what is acceptable for a Spitz tumor, and significant dermal mitotic rates including deep or marginal mitoses (Tables 13 and 14) (Fig. 10). The authors recommend a comprehensive assessment of all such Spitz tumors for risk stratification. Risk stratification permits the general assignment of a risk category of low versus high risk for recurrence and potential regional spread. Some proportion of these lesions are high risk and consequently biologically indeterminate and should be managed with adequate surgical excision and follow-up examinations for recurrence.

Dbridement Except for Skin Ulcer or Cellulitis with CC

Skin cancer is the most common malignancy in the United States, accounting for over 50 of all diagnosed cancers. The majority of skin cancers (more than 90 ) are classified as non-melanoma skin cancers (NMSCs) of which there are two types basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Approximately 75 of skin cancers are BCC SCC is the next most common skin cancer, followed in frequency by melanoma. More than 1.3 million cases of NMSC are diagnosed annually. Other, less frequently occurring skin cancers include skin adnexal tumors, Kaposi's sarcoma, various types of sarcomas, Merkel cell carcinoma, and cutaneous lymphoma, all of which together account for fewer than 1 of NMSCs. BCC is a slow-growing, nonmetastasizing neoplasm of the nonkeratinizing cells of the basal layer of the epidermis, that extends wide and deep if left untreated. If distant metastasis does occur to the bone, brain, lung, and liver, the prognosis is grave. BCC is most frequently found on the head,...

Pigmented Spindle Cell Melanocytic Tumor

The pigmented spindle cell tumor (PSCT) is considered by some to be a pigmented variant of Spitz tumor, and it is clear that clinical and histological overlap occurs between the two lesions. However, the PSCT may show rather distinctive attributes in a large proportion of cases. The lesion usually presents as a small well-defined dark brown to black flat topped papule (Fig. 11A). Histologically, PSCT is a sharply circumscribed mainly intraepidermal proliferation of small heavily pigmen-ted spindle-shaped melanocytes arranged in fascicles or concentric arrays (Figs. 11B-D). A conspicuous feature of PSCT causing considerable confusion with melanoma is pagetoid melanocytosis (Table 16).

Sunburn and Protecting Your Skin from the

Too much exposure to ultraviolet rays from the sun, sunlamps, or tanning beds produces sunburn. The most common symptom of sunburn is red, swollen, and painful skin that can blister. If the sunburn is severe and covers a large portion of your body, you may also experience chills, fever, nausea, and vomiting. Repeated sun exposure also can produce harmful long-term effects, including wrinkling, premature aging of the skin, and skin cancer (see page 428). The most serious type of skin cancer, malignant melanoma (see page 428), is often fatal. People who are most likely to be sunburned and who are most at risk for sun-induced skin cancer are those with fair skin, blue eyes, and red or blond hair, although anyone who spends time outdoors is at risk. The more sun exposure you receive, the more your skin is damaged. Certain medications such as the antibiotic tetracycline, some diuretics (water pills), some tranquilizers, birth control pills, and over-the-counter antihistamines make the skin...

Histological Parameters

The thickness of the clinically thickest lesion (measured from the granular layer to the lower limit of the infiltrate, as in malignant melanoma) (8) has been reported to be significantly correlated with prognosis in CTCL, which is not surprising since the histologically measurable infiltrate correlates with the clinical stage of the disease patchy eczematous lesions histologically show a patchy infiltrate in the papillary dermis in the plaque stage, there is a dense subepidermal infiltrate, filling the papillary dermis, whereas in the tumor stage there is a dense, diffuse infiltrate reaching into or filling the reticular dermis and even the subcutaneous fat. The presence of granulomatous features in CTCL does not have prognostic implications, as cases with aggressive, but also with a prolonged, course have been described (9,10).

Clinicopathologic Correlation

The most important architectural criteria for histopathologic diagnosis of malignant melanoma are breadth (more than one standard 40 x field in diameter), asymmetry, and poor circumscription, and of these, asymmetry is the most important. These microscopic features are reflected clinically in the diameter of malignant melanomas that is greater than that of acquired melanocytic nevi, the asymmetry of melanomas compared to the symmetry of banal nevi, and poor circumscription of malignant melanoma compared to the sharp

Appendix A Table of Primary Lesions and Related Disorders

Actinic keratosis (erythematous) Part V Atypical nevi Part V Common benign nevi (pigmented) Part V Ephelides Part V Erysipelas (erythematous) Part III Erythema multiforme (erythematous) Part III Erythrasma Part III Fixed drug eruption Part III Halo nevi Part V Impetigo (deep red) Part VI Lentigines Part V Malignant melanoma Part V Nodules Basal cell carcinoma (translucent, dome-shaped) Part V Keratoacanthoma (dome-shaped) Part V Malignant melanoma Part V Molluscum (dome-shaped umbilicated) Part II Rosacea (red) Part VI Squamous cell carcinoma (indurated) Part V Verruca vulgaris Part II Papules Malignant melanoma Part V Actinic keratosis (erythematous) Part V Asteatosis Part IV Atopic dermatitis Part IV Erythrasma Part III Malignant melanoma Part V Rosacea (erythematous) Part VI Seborrheic keratosis Part V Senile purpura (purple) Part IV Striae distensae (linear) Part IV Tinea Part III Malignant melanoma Part V Molluscum (tightly-grouped papules) Part II Pityriasis rosea (rosy red)...

Oculodermal Melanocytosis

Pigment Stratum Corneum

Conjunctiva, sclera, and uveal tract. Other ipsilateral involved tissues may be orbital fat and muscles, bone, periorbita, dura, and brain. The nevus tends to be unilateral, but bilateral involvement may occur. Pigmentation is irregular and may occur in small isolated disconnected patches. It may be so pale as to be overlooked on casual observation. Glaucoma can be an associated finding. Intraocular nevi, choroidal malignant melanoma, and orbital melanoma may occur. DIFFERENTIAL DIAGNOSIS The differential diagnosis includes lentigo, malasma, malignant melanoma, osteogenesis imperfecta, ochronosis, and blue nevus. TREATMENT Camouflage make-up may mask the lesion when limited and pale in color. Intense pulsed light therapy or pulsed dye lasers may diminish the degree of pigmentation. Periodic dilated fundus examination is important to rule out uveal melanoma.

Intradermal Nevus Fibrosis

Giant Congenital Melanocytic Nevus

Clark WH Jr, Elder DE, Guerry D IV, et al. A study of tumor progression the precursor lesions of superficial spreading and nodular melanoma. Human Pathol 1984 15 1147-1165. 7. Shors AR, Kim S, White E, et al. Dysplastic naevi with moderate to severe histological dysplasia a risk factor for melanoma. Br J Dermatol 2006 155(5) 988-993. Figure 4 (A) Halo melanocytic nevus. Note symmetry and well-delineated nature of the halo and central nevus. (B) Halo melanocytic nevus. A compound nevus is obscured by a dense lymphocytic infiltrate. The nevus shows maturation and lacks significant atypia. (C) Acral melanocytic nevus. The nevus shows small diameter, symmetry, regular borders, and fairly uniform tan-brown color. (D) Acral melanocytic nevus. A compound nevus demonstrating lentiginous melanocytic hyperplasia and noticeable pagetoid melanocytosis both features raising concern for acral melanoma. However, the lesion has regular nesting of melanocytes and does not show the pronounced...

Melanocytic Neoplasms Neoplasms

This somewhat confusing and archaic term refers to the melanocytes present in melanocytic nevi. Although nevus cells share properties with melanocytes, they are currently thought to be melanocytes in the initial stage of tumor progression to melanoma. These modified melanocytes are characterized by syncytial aggregation in nests within the epidermis and or dermis, loss of dendritic processes, and a progressive sequence of differentiation with descent into the dermis termed maturation. Table 4 Histopathologic and Clinical Criteria for Melanoma Vs. Benign Melanocytic Lesion Table 4 Histopathologic and Clinical Criteria for Melanoma Vs. Benign Melanocytic Lesion

Chloro13Dinitrobenzene 6Chloro13Dinitrobenzene

This substance is one of the strongest primary skin irritant known, and a universal contact allergen. Occupational dermatitis has been reported, but current use is decreasing or performed with completely closed systems. DNCB is sometimes used for topical treatment of alopecia areata, severe warts, and cutaneous metastasis of malignant melanoma.

Recurrentpersistent Melanocytic Nevus

The recurrent (persistent) nevus is defined as the appearance of macular pigmentation within the confines of the clinical scar of a previously biopsied (usually by shave technique) melanocytic nevus, usually after the passage of about six weeks to six months (Fig. 5A). Histologically regenerative and often irregular single cell and nested intraepidermal melanocytic proliferation, sometimes mimicking melanoma, overlies the dermal scar (Table 9) (Fig. 5B). On occasion, the latter intraepidermal component may show cytological atypia of melanocytes (Fig. 5C) and may extend into the dermal cicatrix. Commonly, a residual dermal nevus (corresponding to the original nevus) involves or resides at the base of the scar. It is important to verify the nature of the lesion originally biopsied and exclude malignant melanoma.

Thrombolytic Agents used in Trials and Clinical Practice

Acute stroke.30 Alteplase is expensive, costing approximately 8-10 times more than streptokinase per dose.35'37 In vivo, t-PA is synthesized by the vascular endothelial cells and is considered the physiologic thrombolytic agent that is responsible for most of the body's natural efforts to prevent thrombus propagation. Based on the results of Stroke Trials sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), intravenous thrombolysis with rt-PA was approved as the 'first-ever' effective treatment for ischemic stroke during the first 3 h of symptom onset.36 rt-PA is a sterile purified glycoprotein molecule consisting of 527 amino acids35 that is structurally identical to endogenous t-PA.1,41 It has a molecular weight of 70 000 Da35 and is produced by recombinant technology1,4,35 from a human melanoma cell line.35 The molecule contains five domains finger, epidermal growth factor, kringle 1, kringle 2, and serum protease.2 There are two different forms of t-PA...

Aging Effects by Disease Process

Eczemas Asteatotic dry skin, contact, seborrheic Infections Candidiasis, herpes zoster, onychomycosis, scabies Photodamage Actinic elastosis, colloid milium, Favre-Racouchot syndrome, freckling, photoaging (wrinkling, solar lentigo), poikiloderma of Civatte Premalignant Actinic keratosis, Bowen disease Malignancies BCC, lentigo maligna melanoma, MF, SCC Ulcerations leg, pressure decubitus Other Cutaneous horn, pruritus

Cancer Epidemiology

The genetic basis for cancer is well established through studies with tumor viruses, carcinogenesis models, molecular biology, somatic cell genetics, and genetic epidemiology. Cancer is the result of multiple mutations that occur in oncogenes, tumor suppressors and or DNA repair genes of somatic cells. Although in some cases these mutations can occur in the germ line and are the cause for genetic predisposition, the majority of cancers are sporadic and arise due to somatic mutations in the tumor cells.3-14 Cancer follows a characteristic natural history.1-6 First, normal cells become dysplastic showing subtle morphological abnormalities indicative of the initiation of transformation. Characteristic abnormalities of both form and proliferation then lead to a carcinoma in situ that does not invade the underlying basement membrane of the tissue of origin. These early phases are highly curable and may be detected with screening programs. Localized cancer is a stage I disease when the...

Photoimmunology2

Among the wide-ranging environmental factors affecting human life, ultraviolet (UV) irradiation can be regarded as one of the most significant. Although UV light has an essential impact on terrestrial and aquatic ecology and is a fundamental necessity for the life of humans, animals, and plants, mid-wavelength UVB (290-320 nm) in particular can also exert hazardous effects on health. UV radiation not only plays an instrumental role in the development of skin cancer but also has profound effects on local and systemic inflammatory responses. While studying the biological effects of UVB irradiation, it has become evident that UV exposure can significantly compromise the immune system. The implications of the immunosuppres-sive properties of UV irradiation are manifold because UVB-induced immunosup-pression not only is responsible for the inhibition of protective cell-mediated immunity but also contributes to the initiation, development, and perpetuation of several skin disorders (Fisher...

Apoptosis

Human tumor cells may be defective in the assembly of the apoptosome. This is often the result of a loss of expression of the Apaf-1 protein, as observed in melanomas, leukemias, glioblastoma, and ovarian cancers. Apoptosome assembly may also be blocked by the overexpression of certain chaperones or oncogenes.144 Thus, hsp70 overexpression in breast cancer is correlated with a shorter disease-free survival interval, increased frequency of metastasis, and decreased responsiveness to chemotherapy.145 Expression of the ProToncogene suppresses apotosome formation,146 and increased ProTexpression have been found in human malignancies including lung, hepatocellular, breast, and colon cancers. Finally, caspase activation is a step in the apoptosis pathway that could be blocked by direct interaction with the inhibitors of apoptosis (IAPs). From the IAPs family members (NAIP, c-AIP1, c-IAP2, XIAP, survivin, livin, ILP-2, c-FLIPL, ARC, and BAR), survivin appears to have the most clinically...

Lymphoma

Lymphoma represents 20 of primary small intestinal malignancies. Clinical presentation is variable, depending on whether involvement is primary or secondary, or whether it is preceded by other disorders, such as adult celiac disease, immunoproliferative disease or immunodeficiency syndromes. Radiological appearances mirror the pattern of growth. Enteroclysis can define a wide spectrum of features, including luminal narrowing with mucosal destruction, multiple intra-luminal polypoid filling defects, broad-based ulceration, aneurysmal dilatation, a large excavated mass and fistula formation. Infiltrative lymphomas may cause thickening of the intestinal wall without eliciting a desmoplastic reaction. A combination of different signs is rather frequent and multi-centricity of involvement is seen in almost one fourth of patients. CT appearances of intestinal lymphoma are also variable and may be categorized as aneurysmal, nodular, ulcerative and constrictive, while mesenteric involvement...

Literature Cited

Lee, P.P., Yee, C., Savage, P.A., Fong, L., Brockstedt, D., Weber, J.S., Johnson, D., Swetter, S., Thompson, J., Greenberg, P.D., Roederer, M., and Davis, M.M. 1999. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat. Med. 5 677-685.

Self Examinations

In addition to the tests and screenings that your doctor performs during routine checkups, there are two important self-examinations that you should do regularly to detect any early signs of cancer. The testicle self-examination can help you identify any early signs of cancer of the testicle, and the skin self-examination will aid you in spotting early signs of skin cancer. Examining your own skin is the best way to find skin cancer in the early stages, when it is most treatable. This is especially true of malignant melanoma, the most virulent and sometimes deadly form of skin cancer. A skin self-examination should be a regular part of your health routine. To identify abnormal-looking moles, look for the following signs of skin cancer Malignant melanoma may also cause a mole to change in a number of ways, becoming scaly or crusted oozing or becoming harder or softer. The mole might change in size, or the skin around the mole could redden, swell, bleed, or itch. A red, scaly patch or a...

Molecular Staging

Molecular staging utilizes markers specific to a tumor of interest to minimize missed submicroscopic disease and therefore false negatives. Tyrosinase is an enzyme involved in the synthesis of melanin in normal melanocytes. It is specific to melanoma cells and is not expressed in normal lymph nodes. Use of reverse transcriptase polymerase chain reaction (RT-PCR) to detect tyrosinase mRNA and has been applied in many studies as a marker for melanocytes or melanoma cells. Patients that are histologically positive for melanoma are RT-PCR positive in 94-100 of cases. RT-PCR has also been shown to upstage 13-65 of patients with histologically negative nodes were RT-PCR positive. The vast majority of melanoma patients with histologically positive sentinel lymph nodes (SLN) have no additional positive lymph nodes detected upon completion lymph node dissection (CLND). This information suggests that CLND may not be required for all patients with positive SLN. This study was conducted to...

Response shift

Such changes in patients' expectations (in effect, changes in patients' internal standards) may explain the remarkable finding that many studies show that cancer patients do not report themselves to be more anxious, depressed or unhappy than the non-cancer general population. Indeed, Cassileth etal. 20 found that the mean score on the Mental Health Index of the General Well-being Scale for melanoma patients was actually slightly better than for the general public. Another study by the same group 21 noted that patients who had been living with their illness had better mental health scores than those newly diagnosed and explained this as an adaptation or adjustment to their illness. Such findings may be at odds with the external view of doctors, nurses and patients' friends and families.

Solar Keratoses

Solar (actinic) keratoses present as scaling hyperkeratotic plaques or papules on skin exposed to light. They are most commonly seen on elderly subjects with fair skin who have had high levels of ultraviolet exposure over many years. They may be associated with other signs of photodamage such as yellowing, coarsening, and wrinkling of the skin. Individuals with large numbers of solar keratoses are at increased risk of developing nonmelanoma skin cancer. Histologically, the lesions show epidermal thickening, with abnormal epidermal differentiation and scaling. Solar keratoses are common, and up to 20 of individuals over the age of 60 are affected. Some solar keratoses may resolve spontaneously, but a small proportion may develop into squamous cell carcinoma. Solar keratoses may respond to topical 5 5-fluoro-uracil cream (Efudix) an antimetabolite that inhibits DNA synthesis. This should be applied once or twice daily for 10-14 days, and may cause the lesions and the surrounding skin to...

HIV and AIDS

In addition to CD4-cell counts of less than 200, AIDS is defined by the presence of one or more of 26 conditions, most of which are opportunistic infections that a healthy person could easily fight off. These include highly aggressive forms of certain cancers such as lymphomas (cancers of the immune system) and a type of skin cancer called Kaposi's sarcoma. Other opportunistic infections are

Acquired Melanosis

Histology Conjunctival Nevi

INTRODUCTION Melanocytic lesions of the eyelids run the spectrum from benign nevi and acquired melanosis, to invasive malignant melanoma. Acquired melanosis is very common, with nearly one-third of individuals of European descent having at least one patch of conjunctival melanosis in one eye. It generally appears in middle age. Melanosis consists of abnormally prominent intra-epithelial melanocytes, in contrast to melanocytic nevi where nests of melanocytes occur at the dermal-epidermal junction or wholly within the dermis. Primary acquired melanosis (PAM) is often considered to be pre-malignant melanoma-in-situ. Benign melanosis is more common in young individuals less than 20 years of age, whereas PAM and malignant melanoma pre-dominate in older individuals. Risk factors for malignant change include white race, older age, history of intense sunlight exposure, and cellular atypia within PAM. HISTOPATHOLOGY Primary acquired melanosis (PAM) is classified as lacking atypia or having...

Gallbladder Disease

Gallbladder metastases from malignant melanoma. US shows large, rounded, soft tissue masses bulging into the gallbladder lumen Fig. 8. Gallbladder metastases from malignant melanoma. US shows large, rounded, soft tissue masses bulging into the gallbladder lumen Secondary tumors of the gallbladder are uncommon. Metastases from melanoma may occur within the gallbladder wall and cause typical, rounded mass lesions (Fig. 8).

Photocarcinogenesis

There is a strong association between exposure to reactive oxygen species generating sunlight and human nonmelanoma skin cancer. The relation between UV induction and melanoma is less clear and still controversially discussed in the scientific community. However, recent epidemiological studies and results from animal studies30-36 support the concept that recreational UV-exposure and sunburns with subsequent influx of ROS- generating inflammatory cells into the skin may play an important role in the etiology of cutaneous malignant melanoma. In a recent paper, the long-term combined application of the photosensitizing agent 8-methoxypsoralen and UVA irradiation, widely used for the treatment of psoriasis and other dermatological diseases, resulted in an increased incidence in melanoma development.37 Most likely similar to nonmelanoma skin cancer, melanoma undergoes a multistage development towards the fully malignant phenotype. Operationally, this process can be subdivided into three...

Evaluation

Cancer manifesting as cervical lymphadenopathy will be discovered in the upper aerodigestive tract in about 70 of cases.1 Obviously, the evaluation for the primary should initially focus on this region until other diagnostic information suggests the primary is elsewhere. Specific historic information should be gathered for every patient who has an undiagnosed neck mass suspected to be malignant. Features such as absence of tenderness and progressive enlargement, particularly in a patient with a history of tobacco use or excessive alcohol use, are associated with a higher probability of malignancy. Further questioning about hoarseness, dysphagia, odynophagia, epistaxis, or nasal obstruction may help identify a head and neck primary site. A history of prior malignancy, including skin cancer of the head and neck or removal of pigmented lesions, should be noted. A history of prior head and neck radiation exposure should be elicited. A system review should investigate any gastrointestinal,...

Commentary

Malignant melanoma, squamous cell carcinoma, mycosis fungoides, or other cutaneous T-cell lymphomas are malignant neoplastic diseases. Lentigo maligna (Hutchinson's freckle, Dubreuilh's disease) and parapsoriasis en plaques are prema-lignant conditions, just as some adenomas may progress to colon cancer or angioim-munoblastic lymphadenopathy may evolve into lymphoma (5,6). Progress into frank neoplasia usually requires a period of time in these conditions. Changes in the clinical presentation and more importantly in the histological, phenotypical or geno-typical features indicate this progression. The new molecular technologies such as gene profiling, genomics, and proteomics may allow an even more precise tracking of the disease status. This progression is coupled with a change in prognosis from normal or almost normal life expectancy to reduced survival time.

Integrin Expression

While the expression of some integrins has been linked to malignant cell phenotype, most are considered markers of more differentiated cells.4,5 Integrin a2p1 has been described as the melanoma progression antigen34 and it is upregulated by malignant transformation of osteogenic cells.35 In vitro studies, a2p1 enhances the invasion of cells through type I collagen gels and basement membranes.36,37 Overexpression of a5p1 integrin on hamster ovary cells reduces their tumorigenity.38 While in highly invasive colon carcinoma cells the integrin is expressed in elevated levels compared to less malignant ones, suggesting that in these cells a5p1 integrin contributes to malignant progression.39 Integrin aVp3 is needed for angiogenesis and is often upregulated in cells with invasive and metastatic capacity.40 Antagonists for aVp3 integrin successfully disrupted human tumors transplanted onto chick chorioallantoid membrane.41 Using differential display to evaluate mRNA, it has been shown that...

Promotion

One of the most important players in this respect is the blood supply which provides cancer cells with oxygen, the necessary nutrients, and factors required for replication and survival. A given tissue or organ must have a sufficient blood supply in order to function. No extra blood supply is available though, which will hinder any potential abnormal growth. Cancer cells have to induce the generation of new blood supply in order to sustain their growth. This process is called angiogenesis (as explained already in Chapter 1). Research on the role of angiogenesis for cancer progression has been pioneered by Judah Folkman in the 1960s and 70s Folkman (1971) , and work from his laboratory has been dominating the literature up to now (e.g. Folkman (1995a) Folkman (2002) ). In early experiments, Folk-man and colleagues placed a small number of rabbit melanoma cells on the surface of the rabbit thyroid gland. They observed that the tumor cells

Specific History

Personal and family history relative to malignant melanoma should be obtained when evaluating pigmented nevi. History regarding pregnancy and recent hormonal therapy may also be relevant. When evaluating facial nevi in female subjects, history regarding hair growth and attempts at plucking or removing hair from the mole may be important. Traumatic epilation of hair can produce benign inflammatory changes that are more easily confused with malignancy.

Melanocytic Nevus

Melanocytic Nevus

DIFFERENTIAL DIAGNOSIS The differential diagnosis includes lentigo maligna, malignant melanoma, neurofibroma, balloon cell nevus, papilloma, seborrheic keratosis, inverted follicular keratosis, oculodermal melanocytosis, dermatofibroma, pigmented basal cell carcinoma, and fibrous histiocytoma.

Basal Cell Carcinoma

Keratoacanthomas Rodent Pictures

The nodular-type is the most common form to affect the eyelid and has the classic appearance of a pink or pearly papule or nodule with overlying telangiectatic vessels. As the tumor grows in size a central ulceration may occur surrounded by a rolled border (also known as a rodent ulcer). Cystic varieties may occur. The pigmented basal cell carcinoma is similar, but with brown or black pigmentation. These lesions represent the most common pigmented malignancy on the eyelids, and may resemble malignant melanoma. The morphea or sclerosing type appears as a flat, indurated yellow to pink plaque with ill-defined borders. It may simulate blepharitis or dermatitis. This form of basal cell carcinoma is aggressive and can invade the dermis deeply. It characteristically occurs in the medial canthal region and can invade into the paranasal sinuses, lacrimal system, and orbit. Superficial basal cell carcinomas appear as an erythematous, scaling patch with raised pearly borders....

Metastatic Tumors

INTRODUCTION Eyelid metastases from distant sites are uncommon and account for less than 1 of eyelid tumors. When they do occur the most frequent sites for the primary tumor are breast, cutaneous melanoma, lung, colon, and prostate malignancies. Other primary sites including kidney, thyroid, parotid and trachea, have been reported. Females are affected more than males in a ratio of 4 1 reflecting the fact that breast carcinoma represents more than a third of eyelid metastases. Eyelid metastases usually occur in the setting of a known primary cancer elsewhere in the body, but in rare cases an eyelid tumor can be the presenting sign of an occult carcinoma. CLINICAL PRESENTATION The clinical presentation falls into three main categories the first and most common is a diffuse, painless, noninflammatory, full-thickness, often leathery induration of the lid that may cause ptosis, lid lag, or epiphora. These lesions usually represent scirrhous or desmoplastic metastases from primary lesions...