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Background/objectives: Current literature supports mixed conclusions regarding the outcomes of metastasectomy in Stage IV melanoma. The objective of this national study was to determine the associations of non-primary site surgery with overall survival (OS) in Stage IV melanoma., Methods: The National Cancer Database (NCDB) was queried for all Stage IV melanoma cases diagnosed from 2004 to 2015. Cases missing treatment/staging data or undergoing palliative treatment were excluded (remaining n = 14 034). Patients were separated into 'metastasectomy' (n = 4214, 30.0%) and 'non-metastasectomy' (n = 9820, 70.0%) cohorts. Survival outcomes were analysed using Kaplan-Meier and Cox proportional hazards regressions., Results: On univariate analysis, patients with Stage IV melanoma undergoing metastasectomy (median survival: 15.67 month) had greater overall survival compared with those not receiving non-primary surgery (median survival: 7.13 month; 5-year OS 13.2% vs. 5.6%, P < 0.001). M1a patients that underwent non-primary metastasectomy (median survival: 46.36 month) showed greater survival than those that did not (median survival: 15.31 month; P < 0.001). Metastasectomy was undertaken more frequently for cutaneous (M1a) metastasis compared with non-M1a metastasis (34.6% vs. 28.4%, P < 0.001). Of those receiving metastasectomy, 20.3% also received primary site resection, 33.6% radiation, 26.5% chemotherapy and 31.5% immunotherapy. Controlling for covariates on Cox proportional hazard analysis, all metastasectomy patients demonstrated longer survival [Hazard Ratio = 0.519, P < 0.001; CI 95% (0.495-0.545)] as well as when analysing solely M1a metastasectomy patients [Hazard Ratio = 0.546, P < 0.001; CI 95% (0.456-0.653)], lung (M1b) metastasectomy patients [Hazard Ratio = 0.389, P < 0.001; CI 95% (0.328-0.462)] and visceral (M1c) metastasectomy patients [Hazard Ratio = 0.474, P < 0.001; CI 95% (0.434-0.517)]., Conclusion: Metastasectomy for Stage IV melanoma is independently associated with improved OS in metastatic cases involving the skin, lung and visceral organs., (© 2019 European Academy of Dermatology and Venereology.)

Review Objectives/questions: The objective of the review is to evaluate the effectiveness of Mohs micrographic surgery on the mortality, recurrence and quality of life of patients with nonmelanoma skin cancers when compared with other treatment modalities.Specifically, it aims to examine the effectiveness of Mohs micrographic surgery compared with other treatment modalities such as excisional surgery, curettage and electrodessication and radiation therapy, as well as nonsurgical/chemotherapeutic interventions such as topical 5-fluorouracil and imiquimod immunotherapy in the management of nonmelanoma skin cancers.

Basal cell naevus syndrome is an autosomal dominant disorder that stems from mutations in multiple genes, most commonly patched 1 (PTCH1). The classic triad of symptoms consists of basal cell carcinomas, jaw keratocysts and cerebral calcifications, although there are many other systemic manifestations. Because of the broad range of symptoms and development of several types of tumours, early diagnosis and close monitoring are essential to preserve quality of life. Targeting treatment is often difficult because of tumour prevalence. Newer inhibitors of the hedgehog signalling pathway and proteins involved in proliferative growth have shown therapeutic promise. In addition, preventive medications are being devised. We propose a method for determining appropriate treatment for cutaneous tumours., (© 2015 British Association of Dermatologists.)

Neonatal leukaemia cutis is a significant neoplasm that may represent a cutaneous manifestation of systemic leukaemia, usually of myeloblastic type. Rarely, it may be or appear to be limited to skin, in which case it is called neonatal aleukaemic leukaemia cutis. By definition, it presents within the first 4 weeks of life and often has a 'blueberry muffin baby' appearance of magenta coloured nodules affecting almost any area of the skin, usually sparing mucous membranes, palms and soles. This clinical pattern is more commonly associated with neonatal infections such rubella and toxoplasmosis, and may be evident with other neonatal neoplasms such as neuroblastoma. Due to the morbidity associated with chemotherapy and reported cases of spontaneous remission without systemic progression in those with neonatal aleukaemic leukaemia cutis without 11q23 translocation, the authors not treating the child with chemotherapy, but to simply monitor for fading of the violaceous nodules, and watch for possible signs of systemic leukaemia., (© 2015 European Academy of Dermatology and Venereology.)

Recent years have brought an enhanced understanding of Merkel cell carcinoma (MCC) biology, especially with regard to the Merkel cell polyoma virus as a causative agent. Differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative MCC in morphology; gene expression, miRNA profiles and prognosis have been reported. Origin of MCC is controversial. Presence of neurosecretory granules has suggested that these carcinomas originate from one of the neurocrest derivatives, most probably Merkel cells; the name Merkel cell carcinoma is now widely accepted. Expression of PGP 9.5, chromogranin A and several neuropeptides, initially regarded as specific markers for neural and neuroendocrine cells, has recently been shown in a subset of lymphomas. MCC commonly expresses terminal deoxynucleotidyl transferase and PAX5. Their co-expression under physiologic circumstances is restricted to pro/pre-B cells and pre-B cells. These findings lead to the hypothesis by zur Hausen et al. that MCC originates from early B cells. This review was intended to critically appraise zur Hausen's hypothesis and discuss the possibility that MCC is a heterogenous entity with distinct subtypes., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Kaposi's sarcoma (KS) is a multicentric, malignant neoplasm of a complex and still unclear etiology. We present the case of 87-year-old man referred to our dermatology department with the coexistence of two separate malignances: nodular KS and colon cancer. The patient observed the cutaneous nodules 3 months after colon cancer surgery. The question arises of whether the intestinal malignancy-associated weakened immune system exacerbated what was potentially preexisting but unapparent KS, or actually triggered development of KS.

Infantile haemangiomas, common benign vascular tumours of childhood, are characterized by rapid growth during the first year of life and a slow regression that is usually completed at 7-10 years of age. These tumours are composed of endothelial cells with high mitotic rates and stromal components such as fibroblasts, mast cells and pericytes. Haemangiomas become a challenge when they are part of a syndrome, are located in certain areas of the body or when complications develop. The above-mentioned factors also influence the treatment modality used. However, although there remain many uncertainties regarding management, the beta-adrenergic receptor blocker propranolol is a promising new candidate for first-line systemic therapy. It produces such a dramatic and rapid response that the appearance of an infantile haemangioma should impart expeditious consideration of the risks and benefits of its use.

Solar ultraviolet light electromagnetic waves are a known environmental carcinogenic agent closely associated with the development of skin cancer in light-complexioned individuals. Outdoor workers have higher annual exposure to ultraviolet light. We will review the topic of actinic keratoses among these individuals as this common rudimentary form of superficial cutaneous squamous cell carcinoma is explored in greater detail.

Inflammatory linear verrucous epidermal nevus (ILVEN) is an unusual unilateral eruption with onset usually in infancy or childhood, female predominance, frequent left leg involvement, pruritus, refractoriness to therapy, and a psoriasiform histologic pattern. We review this disorder in describing a 5-year-old girl who also had melanodontia, an association not previously observed to our knowledge.

The Brooke-Spiegler syndrome is an autosomal dominant one characterized by cylindromas, trichoepitheliomas and occasionally spiradenomas. Within a given family, some members may have cylindromas whereas others may have trichoepitheliomas or both. We describe the coexistence of trichoepithelioma papulosum multiplex (also known as epithelioma adenoides cysticum of Brooke) and cylindromas in a 30-year-old man, and discuss the relationship between these two autosomal dominant syndromes.

Purpose: The aim of this work is to evaluate the capability of Tc99m B Dextran as a lymphoscintigraphic agent in the detection of the sentinel node in skin lesions., Materials and Methods: Forty-one patients with melanomas (39) and Merkel cell tumors (2) had perilesional intradermal injection of Tc99m-Dextran 2 hours before surgery. Serial gamma camera images and a handheld gamma probe were used to direct sentinel node biopsy., Results: In 39/41 patients, lymph channels and 52 sentinel nodes (one to three sentinel nodes/patient) could be visualized. In one patient, with a dorsal melanoma, no lymph channels or lymph nodes could be demonstrated on the images and only minimal radioactivity was found in the regional nodes with the probe. Another patient with a facial lesion failed to demonstrate lymph channels or nodes. No adverse reactions were observed., Conclusion: Tc99m-Dextran provided good definition of lymph channels and sentinel node localization, without the risks related to the use of potentially hazardous labeled materials of biological origin.

Trichoepithelioma papulosum multiplex is an uncommon autosomal dominant disorder in which multiple trichoepitheliomas are seen. Its cause may be a defective tumor suppressor gene. Studies have mapped this gene to the 9p21 locus. However, there is a parallel or identical syndrome of multiple trichoepitheliomas and cylindromas. Within a given family, some members may have cyclindromas whereas others may have trichoepitheliomas or a combination of both. Although preliminary evidence suggests a different gene is responsible, it is possible that TPM may be caused by more than two independent genes, with some cases of TPM due to impairment of the gene for cylindromatosis. This entity, as well as other disorders with multiple appendageal tumors, may require clarification and distinction from TPM.

Cutaneous metastatic disease is a prognostically important diagnosis. We report the case of a 64-year-old man who had an uncommon histologic type of lung cancer--a large cell undifferentiated carcinoma, which was metastatic to the skin of the nose. The relative frequency of cutaneous metastasis is similar to that of primary cancers. Cutaneous disease as the first sign of metastasis is most often seen in cancer of the lung. However, its appearance as a large tumor on the nose, which was observed in this case, is unusual.

Over the last 20 years of experience with the AIDS epidemic, we have accumulated a great body of knowledge on Kaposi's sarcoma (KS), a major cause of morbidity and mortality in AIDS patients, especially among homosexual and bisexual men. New antiretroviral therapies, in particular the protease inhibitors, appear to be changing the clinical course of KS. Now, it is not unusual to observe a complete resolution and control of KS with the use of these new agents. As we have begun to unravel the pathogenesis of KS, new treatment modalities have merged targeting some of its pathogenic pathways. Although, chemotherapy remains the cornerstone of its treatment, in particular with the new liposomal preparations, new agents may soon change our approach to KS. Experimental therapies being evaluated in ongoing clinical trials include angiogenesis inhibitors, hormonal therapies, retinoic acid derivatives, and immune modulators such as interleukin 12. Better treatment for HIV, and new experimental therapies targeting the pathogenic mechanisms of KS allow us to envision the future treatment of KS with a certain degree of optimism.

We report a patient with massive facial sarcoidosis. While skin involvement is a common manifestation of sarcoidosis, it is unusual to see it in the dramatic form of cutaneous tumors with mutilation of the central face. There are few reports of tumoral cutaneous sarcoidosis like that of our patient.

The nevus comedonicus (NC) is an uncommon variant of adnexal hamartoma which appears clinically as linear groups of open comedones. Its name may be a misnomer since, according to some, true comedones are not present. NC usually occurs by itself but may be linked with a variety of systemic findings such as skeletal or ocular anomalies. Although the nevus comedonicus is viewed by many as a hamartoma arising from a defective mesoderm, others consider this lesion to be an epidermal nevus involving the hair follicle or an appendageal nevus of sweat ducts.

Cutaneous metastatic disease may be evident in a variety of forms and locations. Anatomically, it may on occasion be confined as localized limb metastases. We report on two patients with localized limb metastases, one from melanoma and the other from Merkel cell carcinoma. Patients with localized limb metastasis have a poor prognosis; however, treatment options not available for generalized cutaneous metastatic disease, such as amputation or isolated limb perfusion with chemotherapeutic agents, can be at times be beneficially employed.

Background: Actinic keratosis (AK) is a common sun-induced precancerous neoplasm confined to the epidermis. It is the initial manifestation of a continuum of clinical and histologic abnormalities that progresses to invasive squamous cell carcinoma (SCC), a disorder that accounts for thousands of preventable deaths in America each year., Objective: The purpose of this work is to describe the actinic keratosis., Methods: This effort was performed by a literature review and analysis., Results: Like SCCs, the vast majority of AKs are asymptomatic. Although some actinic keratoses may become clinically inapparent, possibly either due to immune rejection or simply having their external surface unknowingly scraped off, an untreated AK represents a potentially curable fatal cancer., Conclusions: Each AK should be treated before it progresses to invasive squamous cell carcinoma. Destructive modalities such as cryosurgery using liquid nitrogen and electrodesiccation and curettage are the mainstays of therapy. Each case must be individualized., Learning Objectives: After studying this article, participant should be able to: 1. Understand the concept of an actinic keratosis. 2. Learn how to recognize its clinical manifestations. 3. Be aware of the danger it poses as an easily curable papulonodule that may become a fatal cancer.

Background: Triple extramammary Paget's disease (TEPD) has been considered to be rare in the English literature, and its incidence and characteristics are unclear. There are many therapeutic options for treating extramammary Paget's disease (EPD)., Objective: Our purpose was to investigate how many TEPD cases have been reported previously and to describe their characteristics. We also describe the effectiveness of radiotherapy for them., Methods: We report two TEPD cases, and summarize previously reported TEPD cases together with our cases., Results: Twenty-three TEPD cases have been reported previously. Of these, 19 cases have been in Japan. All but one patient with TEPD were male. Their axillary lesions often showed no eruptions or very slight erythema. Radiotherapy for our cases was effective although the effectiveness of radiotherapy is controversial., Conclusion: In genital Paget's disease bilateral axillae should be examined histologically, even if they show no or slight eruptions. Radiotherapy may be useful for EPD, particularly axillary Paget's disease.

Mycosis fungoides palmaris et plantaris (MFPP) is an uncommon form of mycosis fungoides with main involvement on palms and soles. The lesions may be quite hyperkeratotic. A 56-year-old patient with MFPP was successfully treated with the carbon dioxide (CO2) laser. There was no recurrence of disease at treated sites and excellent cosmetic results were obtained. Treatment with the CO2 laser may be considered a therapeutic option.

Mycosis fungoides (MF) is a type of cutaneous hyperproliferative T-cell disorder that may be localized. Although there is considerable controversy regarding whether MF may originate as a non-neoplastic condition, or even whether MF is a neoplastic condition until late in its course, we have seen a few cases undergo what appeared to us to be a clear progression from an inflammatory disorder to MF. We now report a 32-year-old man with MF most prominent on his right flank and buttock who developed his patches several weeks following, and in the precise locations in which he had experienced, exposure to toxic chemicals in an industrial accident. Because of this history, and because all lesions were transient except for these sites, these permanent lesions were treated with local surgical excision. There was no recurrence of disease at the treated sites, and the progression of MF markedly slowed following surgery, although he has continued to experience multi-focal transient recurrent disease, controlled by a combination of topical and systemic treatments, until the present time. Destructive methods such as excisional surgery or carbon dioxide laser may be considered a therapeutic option for localized MF.

Premalignant keratinocytic keratoses are common, especially in pale-complected persons in whom they appear most often as an actinic keratosis. Although the actinic keratosis has a very low malignant potential, arsenic, tar, thermal, scar, reactional, and radiation keratoses may be more clinically aggressive. This article discusses these premalignant keratinocytic neoplasms.

Kaposi's sarcoma (KS) is an unusual neoplasm that has proved to be an enigma in many ways since its original description by Kaposi in 1872. Its epidemiology has stimulated tremendous interest, amplified markedly in 1981 when it became known as an original defining part of the complex of immune disorders now known as AIDS. The cell of origin, etiology, and therapy for both AIDS-associated and AIDS-unassociated KS continue as matters of intense investigation. In fact, whether it is a reactive hyperplasia or a true malignancy is still a matter of debate, as is the concept of multicentricity versus metastases. Epidemiologic studies suggest that a separate agent apart from HIV-1 may cause KS. A newly postulated KS-associated herpes virus may be linked. The role of the HIV-1 tat gene product, basic fibroblast growth factor, scatter factor, oncostatin M, and other factors that regulate the growth of KS cells are discussed, as well as therapeutic options.

In cutaneous metastatic disease the histologic pattern may be specific or nonspecific. Carcinoma cutis most often shows only the nonspecific pattern of an adenocarcinoma, a squamous cell carcinoma, or an undifferentiated metastatic tumor. However, certain clinical and histologic characteristics may suggest a primary tumor site and type. In addition, special histologic stains and the use of immunohistochemical and electronmicroscopic techniques may also prove valuable in the diagnosis of carcinoma cutis and other cutaneous metastatic diseases.

The relative frequencies of cutaneous metastases are similar to those of the primary cancers; breast, colon, and melanoma are the most frequent in women and lung, colon, and melanoma are the most common in men. Cutaneous metastases represent an opportunity to detect a potentially treatable cancer before other evidence of it is present, to modify therapy as appropriate to the tumor stage, or possibly to use the cutaneous lesion as a source of easily accessible tumor cells for specific therapy. Cutaneous metastatic disease as the first sign of internal cancer is most commonly seen with cancer of the lung, kidney, and ovary.

We report two patients with ecchymotic patches that did not suggest the diagnosis of Kaposi's sarcoma. The principal complaint of one patient was facial and periorbital edema with bilateral periorbital ecchymosis. On his trunk were patches resembling pityriasis rosea-like Kaposi's sarcoma. Both types of lesions proved to be Kaposi's sarcoma on histologic examination. The second patient had scattered ecchymotic lesions, with typical lesions of Kaposi's sarcoma elsewhere on his body. The ecchymotic lesions showed a large amount of extravasated red blood cells and no evidence of amyloid. This variant has not been described previously to our knowledge.

The concept of verrucous carcinoma as a clinicopathologic variant of squamous cell carcinoma is worthy of recognition. It is known by a confusing array of names, such as Ackerman's tumor, Buschke-Loewenstein tumor, florid oral papillomatosis, epithelioma cuniculatum, carcinoma cuniculatum, and cutis papillomatosis carcinoides of Gottron. Its apparent clinical benignity may lead to lengthy periods of misdiagnosis, during which it is likely not to spread to distant lymph nodes, but rather to destroy a nose, mandible, or penis as it slowly but relentlessly extends into underlying tissue. Morphologically warty or verrucous, its relatively bland histologic features are often more suggestive of a verruca vulgaris or pseudoepitheliomatous hyperplasia than of squamous cell carcinoma to those unfamiliar with the diagnosis. Alternatively, when it extends into underlying tissues, it may be mistaken histologically for a benign adnexal tumor or even an epidermoid cyst. Therapy may also be challenging because recurrences are common and concerns about potential anaplastic transformation after radiotherapy are often expressed.

There are two types of sclerosing basal cell carcinoma (BCC), one entirely with this histology and a second with a prominent sclerosing component. Sclerosing BCC and nodular BCC with a sclerosing component often represent a difficult diagnostic and therapeutic challenge.

Actinic keratosis is a common skin disorder in elderly patients with fair complexions. It is caused by exposure to ultraviolet light. If left untreated, actinic keratosis may progress to squamous cell carcinoma. The metastatic potential and prognosis vary with the type and location of the lesion. Several approaches to treatment are available, including local destruction, excisional surgery, Mohs surgery, cryosurgery and radiotherapy.

Kaposi's sarcoma is a unique neoplasm which has emerged as an important element of AIDS in homosexuals but not in others at high risk for AIDS. The biology of this important tumor may be related to cytokines secreted by HIV-infected cells and/or by Kaposi's sarcoma cells themselves. We report 3 patients with multiple keloid-like tumors. These lesions proved to be Kaposi's sarcoma histologically, yet with a unique keloidal component. This variant has not been described previously. It is possible that cytokines that stimulate Kaposi's sarcoma cell growth may also stimulate proliferation of local fibroblasts to produce this variant.

Background: Lymphocytoma cutis is a rare cutaneous eruption that may possess clinical and histologic features resembling malignant lymphoma., Objective: Our purpose was to find a good method to treat patients with lymphocytoma cutis., Methods: Five patients with lymphocytoma cutis were seen; each agreed to cryosurgery., Results: In each patient the lesions responded well to cryosurgery., Conclusion: Cryosurgery appears to be an excellent therapeutic option for patients with lymphocytoma cutis. To our knowledge this is the first time liquid nitrogen has been used to eradicate these lesions.

A 72-year-old man had florid cutaneous papillomatosis (FCP), which is an obligatory paraneoplastic syndrome always associated with an internal malignancy. The cancer, which is usually intraabdominal and most often gastric in origin, evolves parallel to the FCP. This patient is the first case of FCP occurring in association with a lung malignancy. An association of FCP with other signs of internal cancer is common, with malignant acanthosis nigricans usually appearing many times with the sign of Leser-Trélat. FCP, malignant acanthosis nigricans, and the sign of Leser-Trélat are part of a continuum, developing by a common or similar pathogenic pathway due to an underlying malignancy producing a factor possibly similar to human epidermal growth factor.

Sequential thallium-201-chloride and technetium-99m-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) images were obtained in a patient with extracranial metastatic glioblastoma multiforme. Thallium-201 uptake was high (three times the scalp background) in all pathologically confirmed extracranial metastases and moderate (1.6 times scalp background) intracranially, where most biopsy specimens showed gliosis with scattered atypical astrocytes. Technetium-99m-HMPAO uptake was decreased intracranially in the right frontal and parietal lobes which had been irradiated. It was also decreased in one well-encapsulated scalp lesion and high in another scalp mass with less defined borders. Possible mechanisms of tumor uptake of these agents are reviewed.

Bowenoid papulosis is an uncommon genital dysplasia induced by human papillomavirus infection. Clinically, it usually resembles persistent warts, but histologically it may be suggestive of squamous cell carcinoma in situ. This unusual disorder and recent advances in our understanding of it are reviewed.

Verrucous carcinoma of the skin is a rare cancer which tends to appear on the soles of the feet, although it can appear elsewhere on the cutaneous surface. It has not, to our knowledge, been previously reported on a leg amputation stump.