Cutaneous manifestations of genitourinary malignancy

Genitourinary cancers are associated with a range of cutaneous syndromes, which can reflect direct metastatic spread, non-metastatic manifestations of malignancy or the consequences of treatment. More than 220,000 new cases of prostate cancer occur each year in the United States, and thus the associations with cutaneous involvement are quite well documented—rare metastatic spread, vasculitic and hemorrhagic syndromes. Cancers of the bladder and kidney may be associated with direct cutaneous metastases, vasculitic syndromes, hereditary leiomyomatosis, and other familial syndromes. Testicular cancer occasionally metastasizes to the skin but more commonly is associated with the dysplastic nevus (multiple atypical nevus) syndrome. A structured approach to history-taking, examination, and investigation is essential for optimal management, especially when these syndromes precede the diagnosis of a known malignancy. A brief review of the more common iatrogenic cutaneous complications is provided, and includes Raynaud’s phenomenon, purpura, rash, hand-foot syndrome, the consequences of marrow failure, and bleomycin-induced pigmentation.     

Cutaneous Manifestations of Internal Malignancy

The skin often mirrors changes in the organism it envelops. Many neoplastic diseases that affect internal organs display cutaneous manifestations, which may be the presenting signs and symptoms of the underlying malignancy. These may reflect direct involvement of the skin by the tumor (ie, tumor metastasis) or indirect involvement, in which changes in the skin occur in the absence of malignant cells. This review focuses on the latter conditions, which are often referred to as paraneoplastic dermatoses. Included in the discussion are the cutaneous manifestations of inherited syndromes that are associated with an increased risk of internal malignancy, cutaneous changes in patients with hormone‐secreting tumors, and the wide spectrum of proliferative and inflammatory dermatoses that have been associated with internal cancer. CA Cancer J Clin 2009;59:73–98. © 2009 American Cancer Society, Inc.     

The differential diagnosis of familial lentiginosis syndromes

Cutaneous markers of systemic disease are vital for clinicians to recognize. This chapter outlines familial lentiginosis syndromes that include Peutz-Jeghers syndrome, Carney Complex, the PTEN hamartomatous syndromes, and LEOPARD/Noonan syndrome. The inheritance of these syndromes is autosomal dominant; they also share characteristic skin findings that offer a clue to their recognition and treatment. We will discuss the clinical presentation of these disorders, with a focus on the dermatological manifestations, and will provide an update on the molecular mechanisms involved. Recognition of cutaneous markers associated with these rare familial cancer syndromes provides the opportunity to pursue early surveillance for malignancies, as well as genetic counseling.     

Cutaneous manifestations in neuro-oncology: clinically relevant tumor and treatment associated dermatologic findings

Skin findings are a rare but important aspect of the evaluation and management of patients with tumors of the nervous system. Skin findings have the highest prevalence in genetic tumor syndromes termed neuro-genodermatoses, which include neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and tuberous sclerosis. Skin changes are observed in patients with non-syndromic nervous system malignancy, often as a result of pharmacotherapy. The skin may also manifest findings in paraneoplastic conditions that affect the nervous system, providing an early indication of underlying neoplasm, including dermatomyosistis, neuropathic itch, and brachioradial pruritus. In this article, we review the major cutaneous findings in patients with tumors of the brain, spine, and peripheral nervous system focusing on (1) cutaneous manifestations of genetic and sporadic primary nervous system tumor syndromes, and (2) paraneoplastic neurological syndromes with prominent cutaneous features.     

Management of high-risk squamous cell carcinoma of the skin

Cutaneous squamous cell cancer (SCC) is the second most common skin cancer, accounting for one-fifth of all cutaneous malignancies. The majority arise on the head and neck skin, and cumulative UV exposure is thought to be the most likely etiological factor. The majority of deaths from SCC occur in a high-risk subgroup of patients. This high-risk subgroup of patients can be identified as those with tumors greater than 2 cm in diameter; tumor thickness over 4 mm; moderately/poorly differentiated or desmoplastic histological SCC subtype; ear, lip, hand, feet or genital tumor site; presence of perineural or lymphovascular invasion; nodal metastasis at presentation; recurrent SCC; SCC arising from scars or chronic skin disease, for example, chronic ulcers; and SCC arising in immunosuppressed patients. It is important to identify and aggressively treat these patients, as high-risk SCC are associated with a greater mortality and morbidity. This article reviews the diagnosis and management of such high-risk SCC.     

Kaposi's Sarcoma following Chronic Lymphocytic Leukemia: A Rare Entity

Cutaneous manifestations can occur in the wide range of internal malignancy. They can occur by metastases or local spread, direct infiltration, or a site of primary malignancy itself. Sometimes these manifestations are related with an underlying malignancy but they do not contain malignant cells as paraneoplastic dermatological syndromes. Chronic lymphocytic leukemia (CLL) is the most common leukemia all over the world. Cutaneous lesions occur in up to 25% of patients. Most commonly seen cutaneous lesions in CLL are those of infectious or hemorrhagic origin. Skin cancer risk was also increased eightfold in CLL when compared with normal population, so cutaneous lesions in CLL can be the first manifestation of secondary skin malignancy. Herein, we report an interesting case of Kaposi''s sarcoma which was diagnosed during the course of CLL.Key Words: Kaposi''s sarcoma, Chronic lymphocytic leukemia, Secondary malignancy     

Management of high-risk squamous cell carcinoma of the skin

Cutaneous squamous cell cancer (SCC) is the second most common skin cancer, accounting for one-fifth of all cutaneous malignancies. The majority arise on the head and neck skin, and cumulative UV exposure is thought to be the most likely etiological factor. The majority of deaths from SCC occur in a high-risk subgroup of patients. This high-risk subgroup of patients can be identified as those with tumors greater than 2 cm in diameter; tumor thickness over 4 mm; moderately/poorly differentiated or desmoplastic histological SCC subtype; ear, lip, hand, feet or genital tumor site; presence of perineural or lymphovascular invasion; nodal metastasis at presentation; recurrent SCC; SCC arising from scars or chronic skin disease, for example, chronic ulcers; and SCC arising in immunosuppressed patients. It is important to identify and aggressively treat these patients, as high-risk SCC are associated with a greater mortality and morbidity. This article reviews the diagnosis and management of such high-risk SCC.     

Lessons from the skin--cutaneous features of familial cancer

As the molecular basis of disease continues to be elucidated, familial cancer syndromes, which consist of a range of neoplastic and non-neoplastic features, are emerging. The usual pathway of referral to a genetics clinic or familial cancer centre is via an oncologist, when high-risk features that suggest a possible hereditary basis for the presenting cancer are recognised. Traditionally, these high-risk features include more than two family members with similar cancers over two or more generations, a young age of onset, and more than one synchronous or metachronous tumour. These features are effective in ascertaining a substantial proportion of families with hereditary breast and ovarian cancer due to a BRCA mutation, or the more common bowel-cancer predisposition syndromes, such as hereditary non-polyposis colon cancer and familial adenomatous polyposis. However, there are a range of familial cancer syndromes that are not easily detected and that can remain undiagnosed when history and examination are not extended to include non-malignant features. The identification of cutaneous signs associated with rare familial-cancer syndromes provides individuals and their families with the opportunity to undertake early surveillance for malignant and non-malignant complications that might in time be shown to improve outcomes.     

Immunoadsorption therapy for paraneoplastic syndromes

Paraneoplastic neurologic syndromes associated with systemic cancer are being increasingly recognized. Although these syndromes are thought to be immunologically mediated treatment with steroids, immunoglobulin and plasmapharesis has been disappointing. Based on our preliminary experience with the treatment of 6 cases of paraneoplastic neurologic syndromes with protein A immunoadsorption, an institutional, open-arm treatment protocol was established. Since our original report we have treated an additional 7 patients with this method. The 13 cases were accrued over a 2 year period and included 10 women and 3 men with an average age of 63. The paraneoplastic syndromes included 6 cases of cerebellar degeneration, 3 cases of opsoclonus/myoclonus, 3 cases of encephalomyelitis and 1 case of Lambert Eaton myasthenic syndrome. Primary cancers included 4 cases of small cell lung cancer, 2 cases of breast cancer, 2 cases of lymphoma and 1 each of acinic cell cancer, cholangiocarcinoma, Merkel cell cancer, pancreatic adenocarcinoma and rectal cancer. Anti-neuronal antibody status, cerebrospinal fluid and neuroimaging studies as well as cancer staging and treatment protocols were reviewed. Neurologic syndromes were clinically separated into component symptoms and signs for assessment of treatment effect. The treatment goal was a total of 6 sessions of protein A immunoadsorption given twice weekly. Twelve of 13 patients completed therapy and one patient developed cutaneous vasculitis during the second session with termination of treatment. Of the remaining patients 3/12 had a complete response of the primary clinical symptom/sign while 6/12 had a partial response for a total response rate of 9/12 (75%). Toxicity was limited to cutaneous vasculitis in 1 patient and an episode of hemisensory changes in another patient. Current treatment of paraneoplastic neurologic syndromes remains unsatisfactory. Despite the small number of patients in this report, protein A immunoadsorption is a promising therapy which deserves further study in a larger population of patients with paraneoplastic syndromes.     

Skin manifestations associated with kidney cancer

Kidney cancer is a heterogenous disease encompassing several distinct clinicopathologic entities with different underlying molecular aberrations and clinical outcomes. Renal cell carcinoma (RCC) has been shown to evoke immunologic responses that can impact the natural history of disease and clinical presentation. It is important to recognize atypical presentations of disease, including cutaneous manifestations. The incidence of skin metastases from RCC is low, yet needs to be appreciated in the appropriate setting; clinical presentation for these lesions is reviewed briefly. There are several hereditary syndromes that present with well characterized cutaneous lesions and are associated with an increased risk for RCC, including Von Hippel-Lindau and Birt-Hogg-Dubé syndromes. Given that these skin lesions may be the first presenting sign for RCC, timely recognition is of essence and both are discussed in some detail. Several therapeutic options based on immunomodulation are approved for the treatment of advanced RCC. Dermatologic toxicities observed with these agents are also briefly discussed.     

Breast carcinoma and basal cell epithelioma after x-ray therapy for hirsutism.

We report a 60-year-old woman with a history of x-ray therapy for generalized hirsutism at 20 years of age who at the age of 37 years developed the first of numerous basal cell epitheliomas on her trunk, including chest, on a background of radiation damaged skin. At the age of 51 years one of the basal cell epitheliomas was biopsied and an incidental histologic finding was a breast carcinoma. The basal cell epithelioma is clearly linked with x-ray exposure; breast cancer is less so although there is impressive epidemiologic evidence supporting an association between human breast cancer and radiation exposure. In view of an association between thyroid cancer and dermatologic x-ray therapy, further investigation of such an association with breast cancer should be considered. It may be wise to evaluate patients who received dermatologic x-ray exposure to their breasts for possible breast cancer and to consider radiation induced skin damage on or near the skin overlying the thyroid or breasts as a cutaneous marker of internal malignancy or potential internal malignancy.     

乳腺癌合并皮肤转移的治疗进展

恶性肿瘤的皮肤转移相对少见,乳腺癌是女性最常见合并皮肤转移的恶性肿瘤。大部分皮肤转移的乳腺癌均合并其他部位转移,也有少数患者以皮肤转移为首发或唯一表现。单发或少发局限于胸壁的结节型皮肤转移病灶,通过局部为主的综合治疗,部分患者有望获得长期生存或临床治愈;而广泛的皮肤转移以及合并内脏、骨转移的皮肤转移患者,临床上难以治愈,预后不佳,系统治疗联合局部治疗可以减轻肿瘤负荷、缓解痛苦、改善患者生存质量。本文将就乳腺癌合并皮肤转移基本特征及治疗进展进行综述。      

Acupuncture-related rapid dermal spread of breast cancer: a rare case

Many ethnic Chinese patients seek second or adjuvant alternative therapies after breast cancer is diagnosed. Chinese herbs and acupuncture are the most popular methods in East Asia. We present a case of acupuncture manipulation-related cutaneous spread that no literature reported before. Post-acupuncture cutaneous spread was noted in a 54-year-old woman with left neck lymph node recurrence after complete surgery, chemotherapy and radiotherapy treatment. The results of chest computed tomography and skin biopsy showed the metastatic breast cancer in the dermis. Six courses of paclitaxel and gemcitabine followed by trastuzumab were given as therapeutic chemotherapy. The neck mass and cutaneous lesions subsided after 2 courses of chemotherapy. Direct puncture of a metastatic lymph node might increase the incidence of tumor spread on the skin. Therefore, despite the efficacy of complementary and alternative medicine, its safety and possible side effects should be more emphasized.     

Skin lesions in chronic lymphocytic leukemia

Cutaneous lesions occur in up to 25% of patients with chronic lymphocytic leukemia (CLL). These can be caused by either cutaneous seeding by leukemic cells (leukemia cutis, LC) and other malignant diseases or nonmalignant disorders. Skin infiltration with B-lymphocyte CLL manifests as solitary, grouped, or generalized papules, plaques, nodules, or large tumors. Prognosis in CLL patients with LC is rather good and many authors claim that it does not significantly affect patients' survival. However, prognosis is poor in patients in whom LC shows blastic transformation (Richter's syndrome) and when leukemic infiltrations in the skin appear after the diagnosis of CLL. Secondary cutaneous malignancies are also frequent complications in patients with CLL. A higher risk was seen in skin cancer, for which eightfold higher occurrence has been stated. There are some suggestions that alkylating agents and purine analogs may be associated with an increased incidence of secondary malignancies in CLL. Nonspecific, secondary cutaneous lesions are frequently observed in CLL patients. The most common secondary cutaneous changes seen in CLL are those of infectious or hemorrhagic origin. Other secondary lesions present as vasculitis, purpura, generalized pruritus, exfoliative erythroderma, and paraneoplastic pemphigus. An exaggerated reaction to an insect bite and insect bite-like reactions have been also observed.     

Papillomavirus-associated squamous skin cancers following transplant immunosuppression: one Notch closer to control

The frequent occurrence of cutaneous squamous cell carcinomas (SCCs) containing weakly tumorigenic human papillomaviruses (HPVs) following iatrogenic immunosuppression for organ transplantation remains incompletely understood. Here we address this problem in the light of recent insights into (1) the association of low-risk β-HPVs with skin SCCs in the rare genetic syndromes of epidermodysplasia verruciformis and xeroderma pigmentosum, (2) the frequent recovery of post-transplant tumor control on substituting calcineurin-inhibitory with mTOR-inhibitory immunosuppression, (3) the unexpectedly favorable prognosis of node-positive SCCs containing high-risk α-HPVs originating in the activated immune niche of the oropharynx, (4) the rapid occurrence of HPV-negative SCCs in ultraviolet (UV)-damaged skin of melanoma patients receiving Raf-inhibitory drugs, and (5) the selective ability of β-HPV E6 oncoproteins to inhibit Notch tumor-suppressive signaling in cutaneous and mesenchymal tissues. The crosstalk so implied between oncogenic UV-induced mutations, defective host immunity, and β-HPV-dependent stromal-epithelial signaling suggests that immunosuppressants such as calcineurin inhibitors intensify mitogenic signalling in TP53-mutant keratinocytes while also abrogating immune-dependent Notch-mediated tumor repression. This emerging interplay between solar damage, viral homeostasis and immune control makes it timely to reappraise strategies for managing skin SCCs in transplant patients.     

Dermatologic manifestations of internal cancer

The cutaneous manifestations of internal cancer can develop either before or after the presence of an underlying tumor has been established. These signs may result either from the physical presence of tumor cells in the skin or from presumed metabolic effects of tumor cells located at visceral sites. Occasionally, skin involvement in cancer patients is biologically unrelated to the tumor but is instead part of a well-defined inherited syndrome featuring an increased incidence of internal cancer. Whatever the association, inspection of the skin remains an essential part of the complete physical examination.     

Photodynamic therapy for non-melanoma skin cancer

Photodynamic therapy (PDT) involves the administration of a photosensitizing drug and its subsequent activation by light at wavelengths matching the absorption spectrum of the photosensitizer. Because the skin is readily accessible to light-based therapies, PDT with systemic and particularly with topical agents has become important in treating cutaneous disorders. Topical PDT is indicated for treating actinic keratosis, superficial or thin non-melanoma skin cancer, including some cases of nodular basal cell carcinoma, and some cutaneous lymphomas. Advantages of aminolevulinic acid/methyl aminolevulinate PDT include the possibility of simultaneous treatment of multiple tumors and large surface areas, good cosmesis, and minimal morbidity, such as bleeding, scarring, or infection.     

皮肤转移癌62例临床特征分析

目的 探讨皮肤转移癌的临床特征,加深对皮肤转移癌的认识。方法 回顾性分析首都医科大学附属北京友谊医院2002年1月至2015年12月诊治的62例皮肤转移癌患者的临床表现、形态特征、肿瘤来源和发生时间。结果 62例患者中男性40例,女性22例;发病中位年龄为60.0岁（33～82岁）。皮肤转移癌可发生在腹部、胸背部、头皮、四肢等全身皮肤的各个位置,其中以腹壁转移最为多见。原发癌病种最常见于肺癌、胃癌和结直肠癌。病理活检结果显示,40例与原发灶的病理学类型完全相符,3例与原发灶的形态学相符,但肿瘤分化程度不同。1例通过皮肤活检证实为第二原发癌合并皮肤转移癌的诊断。17例在原发癌确诊同时发现皮肤转移,大部分患者在原发癌确诊4年内出现皮肤转移。结论 近年来随着肿瘤发病率的升高,皮肤转移癌亦随之增多,提高对皮肤转移癌的认识,有助于及早明确诊断和治疗,延长患者生存期。     

Genetic testing by cancer site: skin

ABSTRACT: Many hereditary cancer predisposition syndromes are associated with cutaneous findings, both benign and malignant. Dermatological examination and histopathology, when combined with a thorough personal and family medical history, play an important role in the diagnosis of cancer predisposition syndromes. Skin findings are an important diagnostic tool for a variety of cancer syndromes, including Cowden syndrome, Birt-Hogg-Dubé, hereditary leiomyomatosis renal cell carcinoma, and others. This article focuses on the phenotype, medical management, and genetic testing for 4 hereditary cancer syndromes that include cutaneous findings: hereditary melanoma, basal cell nevus syndrome, neurofibromatosis type 1, and neurofibromatosis type 2.