Patterns of skin metastases: a review of 25 years' experience at a single cancer center

Background Skin metastases can be defined as the spread of a tumor from its site of primary origin to the skin. Skin metastasis may be the first sign of advanced cancer or an indicator of cancer recurrence. Objectives To review patient data of 401 skin metastases available from our institution and compare this information to previously published studies. Methods Patient data from the Cancer Registry at RPCI database was reviewed for skin metastasis using vendor software. We included all cases of carcinoma, melanoma, sarcomas, and hematologic malignancies entered during a 25‐year period from January 4, 1985, to March 1, 2010. Data identifying the relationship of tumor incidence, morphology, and skin metastasis was reviewed. A total of 401 patients who had skin metastases at the time of cancer diagnosis or had skin metastases as a recurrent site were included in this study. Extensive literature review was conducted using PubMed for articles relating to skin metastases and its clinical presentation and histological features. Results Breast cancer was the most common cancer to metastasize to the skin (32.7% of all skin metastases seen) followed by bronchus and lung (13.2%), skin (melanoma; 9.5%), lymph nodes (7.5%), oral cavity/pharynx/larynx (6.2%), blood and bone marrow (5.5%), and colorectal (4.2%). The most common histological types of tumors were identified as adenocarcinoma (infiltrating ductal carcinoma [22.7%]), lobular carcinoma (4.7%), and non‐adenocarcinoma (squamous cell carcinoma [12.2%] and malignant melanoma [5.2%]). Conclusions This is the largest review of skin metastases in the United States in the past 25 years. We found the primary cancers that metastasize to the skin have changed in frequency from previous studies. Our data are helpful in indicating which cancers have the strongest predilection for skin metastasis. Identification of these cancers can help both the clinician and patient detect early signs of metastases, which may allow for earlier diagnosis, implementation of therapy, and possible prolonged survival.     

Zosteriform skin metastases: clue to an undiagnosed breast cancer

Cancer metastases represent the most devastating aspect of malignancy, since the mortality of cancer patients is mainly related to the metastatic behavior of the primary neoplasm. Skin metastases are usually late events in the course of tumor progression. Excluding melanoma, the most common tumor to metastasize to the skin is breast cancer. Patients who develop cutaneous metastases rarely present with a zosteriform distribution. Herein, we present a 60-year-old female, an undiagnosed case of breast cancer, with zosteriform metastases along her right T2-T3 dermatome.     

Pattern of skin cancer among Saudi patients attending a tertiary care center in Dhahran,Eastern Province of Saudi Arabia. A 20‐year retrospective study

Skin cancer is the ninth most common malignancy in Saudi Arabia. It represented 3.2% of all newly diagnosed cancer cases in the year 2010. The aim of this study was to determine the epidemiology of skin cancer in relation to age, sex, and anatomic location among Saudi patients attending the Johns Hopkins Aramco Healthcare center in Dhahran, Eastern province of Saudi Arabia. We retrospectively reviewed the surgical pathology records of Saudi nationals from 1995 to 2014 at the Johns Hopkins Aramco Healthcare center, which directly provides for the healthcare needs of Saudi Aramco company employees and dependents in the Eastern Province of Saudi Arabia. Tumor metastases to skin, skin involvement by primary breast carcinoma, and B‐cell leukemia/lymphoma with secondary involvement by skin were excluded. The total number of primary skin tumors was 204. The commonest cutaneous malignancies were basal cell carcinoma (36%) followed by squamous cell carcinoma (23%), with the head and neck being the commonest location for both tumors. Mycosis fungoides (MF) was the third most common malignancy (11%). Malignant melanoma was the fourth commonest skin malignancy (7%) with the lower extremities being the commonest location. The four most common skin cancers in our tertiary center in the Eastern Province of Saudi Arabia were squamous cell carcinoma, basal cell carcinoma, MF, and malignant melanoma. Other regions of Saudi Arabia report a similar pattern of skin cancers as our center, with MF having a higher frequency at our center.     

Metástasis cutáneas de cáncer de mama: 8 años de revisión en un centro de tercera complejidad

Background and objectivesBreast cancer is the most common cause of cutaneous metastases. In our review of the literature, we found no studies that have investigated the prevalence of cutaneous metastases from breast cancer in Latin America or compared survival in relation to the site of cutaneous involvement or the presence of visceral metastases.The aims of this study were to characterize the prevalence and clinical features of cutaneous metastases from breast cancer and analyze survival in relation to site of involvement and the concomitant presence of visceral metastases.Materials and methodsRetrospective cohort study. We evaluated patients with breast cancer and histologically confirmed cutaneous metastases.ResultsData from 914 patients with breast cancer seen between 2007 and 2014 were analyzed. Thirty-one of the patients, all women, had cutaneous metastases (prevalence, 3.4%; 95% CI, 2.3%-4.7%). The most common form of metástasis was nodular, metachronous, and asymptomatic.There were discrepancies between the immunohistochemical findings for the primary tumor and the metastases in 5 of 21 women. The metastases were locorregional in 23 patients and distant in 8. No differences were observed between patients with locorregional and distant metastases for survival after diagnosis of the primary tumor (median of 4.7 vs. 4.8 years; P=.085) or the cutaneous metastases (median of 2.9 vs. 1.1 years, P=.06). Women with a simultaneous diagnosis of cutaneous and visceral metastases had the shortest survival.ConclusionsThis is the first study in Latin America to estimate the prevalence of cutaneous metastases from breast cancer and we found it to be lower than rates reported for other parts of the world.     

Cutaneous metastases from internal malignancies: a clinicopathologic and immunohistochemical review

Skin metastases occur in 0.6%-10.4% of all patients with cancer and represent 2% of all skin tumors. Skin metastases from visceral malignancies are important for dermatologists and dermatopathologists because of their variable clinical appearance and presentation, frequent delay and failure in their diagnosis, relative proportion of different internal malignancies metastasizing to the skin, and impact on morbidity, prognosis, and treatment. Another factor to take into account is that cutaneous metastasis may be the first sign of clinically silent visceral cancer. The relative frequencies of metastatic skin disease tend to correlate with the frequency of the different types of primary cancer in each sex. Thus, women with skin metastases have the following distribution in decreasing order of frequency of primary malignancies: breast, ovary, oral cavity, lung, and large intestine. In men, the distribution is as follows: lung, large intestine, oral cavity, kidney, breast, esophagus, pancreas, stomach, and liver. A wide morphologic spectrum of clinical appearances has been described in cutaneous metastases. This variable clinical morphology included nodules, papules, plaques, tumors, and ulcers. From a histopathologic point of view, there are 4 main morphologic patterns of cutaneous metastases involving the dermis, namely, nodular, infiltrative, diffuse, and intravascular. Generally, cutaneous metastases herald a poor prognosis. The average survival time of patients with skin metastases is a few months. In this article, we review the clinicopathologic and immunohistochemical characteristics of cutaneous metastases from internal malignancies, classify the most common cutaneous metastases, and identify studies that may assist in diagnosing the origin of a cutaneous metastasis.     

Clinical manifestations of cutaneous metastases: a review with special emphasis on cutaneous metastases mimicking keratoacanthoma

Approximately 5% of oncology patients develop cutaneous metastases, with only a small number of these patients (less than 1%) having metastatic skin lesions as the first sign of their visceral cancer. Metastases tend to occur on skin surfaces in the vicinity of the primary tumor. However, any site may be affected by cutaneous metastases. Skin metastases can present with several morphologies including, albeit rarely, keratoacanthoma-like lesions. Keratoacanthoma is a keratinous tumor that morphologically appears as a nodule with a central keratin-filled crater. This article reviews the characteristics of oncology patients whose cutaneous metastases mimicked a keratoacanthoma, including illustrations from our patient, a 53-year-old Caucasian man whose metastatic esophageal adenocarcinoma not only presented with a keratoacanthoma-like tumor on his upper lip but also a forehead macule and a scalp nodule. We also report keratoacanthoma-like presentations from literature cases of breast cancer, chondrosarcoma, and pulmonary malignancies. The lesions were discovered 3-24 months after diagnosis of visceral cancer and led to the discovery of unsuspected lung cancer in two patients. Most of the patients (60%) died within 2 months of discovery of the keratoacanthoma-like cutaneous metastases. We also reviewed the literature and discuss other morphologies of cutaneous metastases in patients whose primary tumors were in the breast, lung, and esophagus. In addition, we review from the literature other examples of tumors that present as metastatic nodules on the scalp. The possibility of cutaneous metastasis should be entertained and pathologic evaluation should be considered in an oncology patient with underlying visceral malignancy who develops a keratoacanthoma-like lesion.     

Zosteriform metastatic skin cancer: report of three cases and review of the literature.

BACKGROUND: Metastatic skin cancer is a rare complication of internal malignancies. Patients who do develop skin metastases seldom present with a zosteriform distribution. OBJECTIVE: To elucidate the characteristics of zosteriform metastatic skin cancer, 15 cases from the medical literature and 3 cases seen in our clinic were reviewed clinically and histopathologically. METHODS: The age and sex of each patient, site of the primary tumor, pathology of primary and metastatic lesions, location of the skin cancer and presence of pain were determined for the 18 cases of zosteriform skin cancer. RESULTS: The most frequent site of the primary tumor was the breast (4 cases), ovary or lung (3 cases each), prostate, bladder or stomach (2 cases each) and uterus or colon (1 case each). The most common site of the skin metastases was the chest wall (8 cases) and abdominal wall (7 cases). The histology of the primary lesion was compatible with adenocarcinoma (10 cases), transitional cell carcinoma or serous papillary cystadenocarcinoma (2 cases each) and ductal carcinoma (1 case). Eleven cases developed on the nearest covering skin and/or on the same side as the primary tumor. Eleven patients complained of pain. Seven cases were treated as herpes zoster with antiviral agents. CONCLUSION: Approximately 50% of cases of metastatic skin cancer developed on the nearest skin covering and on the same side as the primary tumor. This evidence may be useful when trying to pinpoint the location of the primary tumor. One third of patients with skin metastases were misdiagnosed and their lesions were treated initially as herpes zoster. When a band-like eruption is seen in patients with internal malignancies, the possibility of metastatic skin lesions should be considered. A skin biopsy is necessary to confirm the diagnosis.     

HEPATOCELLULAR CARCINOMA INVASIVE TO CHEST WALL

An 88-year-old white man developed hepatocellular carcinoma forming a large subcutaneous mass by direct invasion of the posterior chest wall. Forty-seven cases of cutaneous metastases from primary liver cancer have been reported. These cutaneous metastases showed protean morphologic features with the face and scalp being the most common sites of involvement. The metastatic lesions may be the presenting sign of the cancer. Average survival, after development of a skin metastasis, was 5 months. Skin metastases from primary liver cancer are being reported more frequently. This is due, in part, to more prolonged survival of liver cancer patients, which allows development of skin metastases, and also due to increased awareness by the clinician.     

Osteosarcoma of the skin

Background Osteosarcoma is a common malignancy, although skin metastasis is rare. We sought to review the incidence, epidemiology, risk factors, and prognosis of osteosarcoma with skin involvement. Methods We conducted a retrospective chart review that covered 30 years and involved clinic patients younger than 18 years who had cutaneous metastases of osteosarcoma. The main outcome measure was histologic documentation of both primary tumor and metastatic lesion in the skin. Results Two patients were found to have osteosarcoma with skin involvement. No unifying factors were identified. Conclusions Although osteosarcoma is a common malignancy with frequent metastases, involvement of the skin is rare. Further studies to identify risk factors and subsequent prognosis are necessary. Nevertheless, unidentifiable skin lesions in a patient with a history of osteosarcoma should be investigated to rule out tumor metastasis, regardless of cancer status.     

Skin metastasis: a pathologist's perspective

Skin metastasis is defined as the spread of malignant cells from a primary malignancy to the skin. It is one manifestation of systemic spread of cancer. The tumor cells originate either from an internal malignancy or from a primary skin cancer. This study presents a literature review concerning these issues as well as this author's experience encountered throughout 19 years of surgical pathology and dermatopathology practice. Several conclusions are evident. Generally, skin metastases are encountered in 0.7–9% of all patients with cancer and as such the skin is an uncommon site of metastatic disease when compared to other organs. There is usually a long‐time lag between the diagnosis of the primary malignancy and the recognition of the skin metastases. However, these metastases may be the first indication of the clinically silent visceral malignancies. The regional distribution of the skin metastasis, although not always predictable, is related to the location of the primary malignancy and the mechanism of metastatic spread. The relative frequency of skin metastasis correlates with the type of primary cancer, which occurs in each sex. For instance, lung and breast carcinomas are the most common primaries that send skin metastasis in men and women, respectively. The head and neck region and the anterior chest are the areas of greatest predilection in men. The anterior chest wall and the abdomen are the most commonly involved sites in women. Skin metastases usually appear as non‐specific groups of discrete firm painless nodules that emerge rapidly without any explanation. They vary in size from so tiny as to be of ‘miliary lesions' to as large as ‘Hen’s egg size’. Some skin metastasis may mimic specific dermatological conditions such as cutaneous cyst, dermatofibroma, pyogenic granuloma, hemangioma, papular eruptions, herpes zoster eruptions, rapidly infiltrating plaques, alopecic patches, cellulitis and erysipelas. Histologically, the skin metastases usually show features reminiscent of the primary malignancy, but with variable degrees of differentiation. Molecularly, skin metastasis is an organized, non‐random and organ‐selective process orchestrated by interaction among several heterogeneous molecules, which are largely unknown. Metastasis to the skin is often a pre‐terminal event that heralds poor outcome. Hussein MRA. Skin metastasis: a pathologist's perspective.     

Multinodular Cutaneous Spread in Neuroendocrine Tumor of the Breast

Carcinoid tumors are the most common type of neuroendocrine tumors with an incidence of 1.5 per 100 000 of the population. Skin manifestations of carcinoid tumors include those associated with the carcinoid syndrome and sequelae from metastatic disease. Carcinoid tumors in the breast, which were first described in 1977, are rare and may present either as primary or metastatic lesions. The existence of primary breast carcinoid tumors is controversial, however, and, if they do exist, would account for <1% of primary breast cancers. We report the case of a 76-year-old woman who presented to the M.D. Anderson Cancer Center with a long-standing history of a breast lump. Core biopsy of the mass and left axillary lymph node aspiration revealed neuroendocrine tumor of the breast, which stained positive for synaptophysin and chromogranin. Subsequently, the patient developed a left-sided pleural effusion, and a further work-up revealed metastases to the lung parenchyma and pleural space. Three years after her diagnosis, she complained of a persistent, erythematous thickening of skin over the surface of her left inferior breast, which had been present for 1 year. On examination, multiple erythematous grouped nodules arranged in an oval pattern were present. A punch biopsy from one of the nodules revealed invasive low-grade carcinoma with neuroendocrine features similar to those in her prior breast core biopsy. The tumor was seen to be infiltrating the dermis. This is a unique case of a neuroendocrine tumor of the breast with cutaneous spread. The number of reported cases of neuroendocrine tumors with cutaneous involvement remains small.     

Cutaneous metastasis of invasive ductal carcinoma of the breast to an infusaport site

Cutaneous metastasis of a primary internal malignancy is a relatively common phenomenon, occurring in up to 10% of patients with noncutaneous cancer. Cutaneous metastasis can occur via direct extension, hematologic or lymphatic dissemination, or surgical implantation. The most common internal malignancy associated with the development of cutaneous metastases in females is breast cancer. We present a patient with widely metastatic invasive ductal carcinoma of the breast, status postpalliative mastectomy and chest wall coverage with a vertical rectus abdominus myocutaneous flap, who acquired cellulitis and, subsequently, noncontiguous cutaneous metastasis of her breast cancer to the site of her central venous access device (ie, infusaport). We hypothesize that the local inflammation associated with her recent bout of cellulitis and operations, in conjunction with the presence of a foreign body, may have predisposed the infusaport site to seeding by metastatic tumor cells. This case highlights the importance of considering cutaneous metastasis in the differential diagnosis of new skin eruptions in patients with cancer.     

Breast carcinoma en Cuirasse - Case report

Cutaneous metastasis is a phenomenon that results from a tumor spreading via lymphatic or vascular embolization, direct implant during surgery or skin involvement by contiguity. The primary malignant tumor that most commonly metastasizes to the skin in women is breast cancer, which can be manifested through papulonodular lesions, erysipeloid or sclerodermiform infiltration, en cuirasse. We report the case of a female patient, 78 years old, with papular, scaly and confluent lesions in the right breast for one year, progressing to edema and skin infiltration, reduction of breast volume and plaque en cuirasse, and similar lesions in the contralateral breast and abdomen for four months. The pathological diagnosis was invasive ductal breast carcinoma with Paget-like foci, epidermal skin metastases and lymphatic embolization.     

Metástasis cutáneas de tumores sólidos. Estudio descriptivo retrospectivo

Introduction

Cutaneous metastases are a rare event compared with other metastases. Their incidence is estimated between 0.7% and 9% of patients with cancer. Their presence always indicates a disseminated malignant disease and could also be the first manifestation of a tumor, appearing simultaneously or after a diagnosis of cancer.

Objectives

To describe the epidemiological and clinical characteristics of cutaneous metastases in our hospital.

Material and method

We performed an observational retrospective study. We included all patients with cutaneous metastases diagnosed in the Dermatology Service of our hospital during a 7-year period. Patients with metastases from sarcomas, melanomas and hematologic malignances were excluded.

Results

We studied 102 patients with cutaneous metastases. The primary tumor was identified in 87 patients (85%). The most frequent tumors were breast cancer in women (48%) and lung cancer in men (11%). Cutaneous metastases were the first sign of malignancy in 12 patients (11%). The predominant clinical form was the nodular form. The most common localization of the metastases was the thoracic region. The most common histologic diagnosis was adenocarcinoma. The mean survival after the development of metastases was 22.1 months.

Conclusion

There is an association between the frequency of cutaneous metastases and the most frequent malignancies in each sex.Our results were similar to those of other studies regarding age, sex distribution, the predominant clinical form, location, and histological diagnosis of cutaneous metastases.     

Cutaneous metastasis from lung cancer: Retrospective analysis of 30 patients

Lung carcinoma is one of the most frequent sources of skin metastases in male patients. Our objective was to analyse the clinical and pathological features of 30 patients with skin metastases from lung carcinoma. Cutaneous biopsies codified as ‘skin metastasis from lung carcinoma’ during 1988–2009 at Bellvitge Hospital (Barcelona, Spain) were reviewed. The histological types of 30 lung carcinomas (29 men, 1 woman) were squamous cell carcinoma (10 cases), undifferentiated carcinoma (7), adenocarcinoma (6), small cell carcinoma (5) and large cell carcinoma (2). The most frequent clinical presentation was as a solitary nodule (16 cases), and the most frequent site was the head (13 cases). Cutaneous metastases were present at the time of diagnosis of the lung primary tumour in 66% of cases. Skin biopsy might be helpful to establish the histological type of tumour, and thus help with therapeutic decision‐making. Cutaneous metastases from lung cancer remain a poor prognostic feature.     

Skin metastases of lung cancer

Skin metastases of lung cancer are rare. In over a 3-year period we found only 14 cases of skin metastases among 1,614 patients with lung cancer admitted to the University Clinic of Respiratory and Allergic Diseases in Golnik. The metastases are usually manifested on the skin of the chest. Skin metastases are symptoms of progressive disease, and usually a sign of a poor prognosis. The median survival time of lung cancer patients with skin metastases was 85 days from the time of detection of the skin lesion. Because skin metastases can be the first sign of the disease, the entire skin should be carefully inspected whenever malignant disease is suspected.     

以皮肤表现首诊的胃癌一例并发皮肤转移癌临床分析

目的统计我院皮肤科病理室皮肤转移癌患者资料,分析其临床特点,加深对皮肤转移癌的认识。方法报告1例以皮肤表现首诊的胃印戒细胞癌,并综合2011年1月—2016年1月的皮肤转移癌资料,分析患者年龄、性别、皮损形态特征和发生部位等特点,以及原发肿瘤的类型及皮肤转移癌与原发肿瘤发生时间的关系。结果共统计皮肤转移癌14例,占我科皮肤病理室组织病理切片总数0.24%(14/5 955例),其中男5例(36%),女9例(64%),平均年龄(57.46±12.02)岁;9例女患者中,原发于乳腺癌7例(77.8%),胃癌1例,未明确原发灶1例;5例男患者中,原发于肺癌3例(60.0%),食管癌1例,未明确原发灶1例。所有患者中以皮肤表现为首发症状3例,皮肤转移癌首发率21.4%(3/14);11例患者表现为浸润性红斑及红斑基础上的丘疹、结节,2例表现为头皮孤立结节,1例表现为胸腹部多发结节。14例皮损均分布于头颈部及胸腹部。3例患者的免疫组化显示为低分化腺癌,其中1例经及时化疗后皮损基本消失,随访1年已临床痊愈。结论皮肤转移癌发生率低,以皮肤表现首诊的转移癌少见。对于皮肤转移癌早发现、早诊断、早治疗可一定程度改善预后。     

皮肤转移癌62例临床及组织病理分析

回顾性分析我院皮肤科2010年1月至2021年1月期间62例皮肤转移癌患者的临床及组织病理特征。结果示62例患者中,男34例(54.8%),女28例(45.2%),发病平均年龄为(59.2±12.5)岁(41～89岁)。患者就诊时间中位数为2个月。45例患者仅有一个转移灶,17例有两个或以上转移灶。好发部位依次为胸部(18例),头部(14例),四肢(12例)。皮损表现多为结节、包块(49例),其次红斑(9例)、丘疹(4例)。原发肿瘤中最多的为转移性腺癌56例(90.3%),其次为转移性鳞癌4例(6.5%),另2例为小细胞癌。男性以肺癌最常见,女性以乳腺癌最多见。62例病例中19例误诊为其他疾病,首诊误诊率为30.6%。皮肤转移癌临床上容易误诊,应提高对皮肤转移癌的警惕性。     

Cutaneous angiosarcoma: a case series with prognostic correlation

BACKGROUND: Cutaneous angiosarcoma (CA) is a rare and aggressive endothelial-derived sarcoma. Few large studies have examined the clinicopathologic and prognostic attributes of CA. OBJECTIVES: We sought to discern the potential prognostic significance of a variety of demographic features (i.e., age, sex, location), histologic attributes (i.e., depth of invasion, tumor necrosis, tumor cell morphology, margin status, mitoses), and follow-up data (i.e., tumor recurrence, metastases) in CA. METHODS: The statistical influence of age, sex, anatomic location, tumor depth of invasion, tumor cell morphology, presence or absence of necrosis, number of mitoses, and margin status on time to tumor recurrence and metastases were examined in a series of 47 patients with CA. Angiosarcoma arising within the breast, in a previously irradiated anatomic site, and a pre-existing vascular malformation or one associated with a lymphedematous extremity were excluded from study. RESULTS: Most of the patients were men (76%), with an average age of 75.1 years (range: 59-92 years). The most common location was the head and neck region (96%). The most common presentation was of a rapidly expanding erythematous patch, and the most common clinical impression was angiosarcoma. The average external diameter of the tumor was 5.3 cm (range: 1.1-8.9 cm). The most common histologic pattern was characterized by anastomosing dissecting sinusoids lined by atypical endothelial cells (64%) with 15% of cases showing a diffuse epithelioid or spindle cell proliferation and 21% showing a mixture of the 2 histologic patterns. The average depth of tumor invasion was 2.86 mm (range: 1.8->6.0 mm). Of the tumors, 78% had a mitotic rate that exceeded 3/mm(2). Follow-up was available in 37 of the patients and ranged from 6 to 65 months. The 5-year local recurrence rate was 84% and the overall 5-year survival was 34%. Most patients died as a result of their disease with widespread pulmonary, cardiac, and/or brain metastases. CONCLUSIONS: Of the gross and histologic features, external diameter (>5 cm), depth of invasion (>3 mm), mitotic rate (>3 HPF), positive surgical margins, tumor recurrence, and metastases correlated with adverse outcome by univariate analysis and, with the exception of mitotic rate, by multivariate analysis. Of the foregoing, tumor diameter, depth of invasion, positive margins, metastases, and tumor recurrence were the most robust predictors of outcome. None of the demographic factors was associated with outcome. This study confirms the poor prognosis of patients with CA. Among all demographic and histologic patterns examined for prognostic significance, tumor diameter, tumor depth of invasion, margin status, tumor recurrence, and metastases emerged as the most important determinants of outcome.