Abstract
Background: Cutaneous metastases from lung cancer are uncommon; they can be the presenting sign of an unknown malignancy. Case Report: We present a 53-year-old man with a presternal mass that proved to be a cutaneous metastasis revealing an underlying lung adenocarcinoma. We searched the relevant literature and present a review of the main clinical and pathological features of this type of cutaneous metastasis. Conclusion: Skin metastases are a rare manifestation of an underlying lung cancer, of which they can be the initial manifestation. Recognition of these metastases is important to promptly introduce an appropriate treatment.
Carcinomas of the lung usually metastasize to the nervous system, adrenal glands, liver, bone, and kidneys, and only rarely to the skin. Cutaneous metastases develop in 1-12% of patients with advanced lung cancer (1, 2). Remarkably, skin metastases from lung carcinomas develop more rapidly compared with other primary malignancies (3); they may be synchronous or occur before the diagnosis of the primary tumour, and usually herald a poor outcome.
We report here a patient with a painless presternal mass diagnosed as metastatic adenocarcinoma from a hitherto unknown lung carcinoma. We performed a PUBMED search using the keywords “skin metastasis lung cancer”, “cutaneous metastasis of lung cancer”, “lung adenocarcinoma metastasis to the skin”, “lung metastasis”, “pulmonary metastasis” and “skin lesion in lung cancer”, which yielded 64 articles reporting 101 patients. Based on these, we present a brief review of the salient clinicopathologic features of this specific type of cutaneous metastasis.
Case Report
A 53-year-old man who had been a heavy smoker with 30 pack-years and had a history of right eye blindness presented to our department for a painless presternal mass, which had progressively grown over the previous 6 months. The patient was in good general condition and did not mention weight loss, fever, anorexia, or respiratory symptoms; he was not receiving any medication or herbal supplements. Physical examination showed an erythematous, mobile, and tender presternal mass measuring 5×4 cm (Figure 1). Complete physical examination revealed no other skin lesions. A previous ultrasound examination had shown a non-specific mass consistent with a cyst. Given the rapid progression of the lesion over the previous months, we performed a diagnostic skin biopsy. Histological examination showed, within the mid and deep dermis, a tumour made of medium-sized, round cells with eosinophilic cytoplasm and large, hyperchromatic nuclei. The cells were arranged in solid nodules, containing rare gland-like cavities (Figure 2); by immunohistochemistry, they expressed diffusely keratins (AE1/AE3), including keratin 7 (Figure 3), and more weakly PD-L1 (7% of cells). They were negative for keratin 20, MART-1/Melan-A, gp100/HMB-45, desmin, CD45, ROS1, TTF-1, napsin, CD56, synaptophysin, and ALK. These features were consistent with an undifferentiated, probably metastatic, adenocarcinoma. The presternal mass was subsequently totally excised. Macroscopically it consisted of a whitish nodule with a partly necrotic centre; microscopically it showed features similar to the ones observed in the initial partial biopsy. A complementary immunohistochemical study showed strong positivity for GATA-3 and more weak positivity for keratins 5/6 and progesterone receptors (5% of cells). The tumour was negative for SOX-10, p40, p63, PAX-8, and oestrogen receptors. Altogether, these morphologic and immunohistochemical features favoured the diagnosis of undifferentiated adenocarcinoma.
Macroscopic appearance of the presternal metastatic mass.
Microscopically, the tumour is made of undifferentiated round-to-oval cells with an eosinophilic cytoplasm and large, hyperchromatic nuclei. Note a gland-like cavity in the right border of the panel (haematoxylin-eosin stain, original magnification ×250).
The tumour cells express diffuse cytoplasmic reactivity for keratin 7 (immunoperoxidase revealed with diaminobenzidine, counterstaining with Mayer’s haematoxylin, original magnification ×250).
The patient underwent a whole-body computed tomography scan; this revealed two lesions on the left upper lung which, on positron emission tomography imaging, demonstrated strong uptake of the radiotracer. Respiratory functional explorations revealed a moderate obstructive deficit (forced expiratory/vital capacity ratio 58%, 53% diffusing capacity for CO). The lung tumour was surgically excised. Molecular analysis showed that the lung and the cutaneous carcinoma contained the same gene variants, namely TP53, ATRX, RADS1D, and SMARCA4. Based on these clinical and laboratory findings, the patient’s cutaneous tumour was diagnosed as metastasis from the lung adenocarcinoma. Chemotherapy with Cisplatin Alimta was initiated. The patient is under follow-up 13 months after the diagnosis.
Discussion
Cutaneous metastasis may be the first manifestation of a clinically occult visceral malignancy. Lung cancers metastasize to the skin in 1-12% of cases, and this event is associated with a high rate of mortality (4). Lung carcinomas are more frequent in men than in women (5). Our patient had no known primary cancer, and the diagnosis of metastatic carcinoma relied on physical examination, immunohistochemical studies, tumour markers, and imaging.
Our literature search revealed 101 cases of cutaneous metastasis of lung cancer (Table I). The mean patients’ age was 65±8.2 years. A strong male predominance was found (sex ratio: 5:1). Considering those patients where the history of smoking was known, 52/57 (i.e., 91%) were smokers. Most skin metastases were single (55.4%) and their commonest clinical appearance was a nodule or mass (75.2%). The metastatic tumour can be located anywhere on the body, although it usually affects areas close to the primary tumour (1); consequently, the trunk is the body site most commonly involved, followed by the head/neck region. Cancers of the upper lobes of the lungs have a greater tendency to metastasize to the skin (6). The exact pathogenesis of this tropism is still unknown. Our literature review revealed that 32.6% of the primary lung carcinomas were located in the upper lobes.
Clinical characteristics of patients with cutaneous metastases from lung cancer.
The classification of lung carcinomas is based on morphological features, as well as immunohistochemical and molecular biology data (7). The relationship between the histological subtype of lung cancer and the development of cutaneous metastasis has been debated (8). It has been claimed that adenocarcinomas of the lung show the greatest tendency to metastasize to the skin, followed by squamous cell carcinomas and large cell carcinomas (9). Accordingly, our literature review confirmed that adenocarcinoma is the predominant type of cutaneous spread in patients with lung cancer (51.4%), followed by squamous cell carcinoma (27.7%), undifferentiated carcinoma (11.8%), small-cell carcinoma (6.9%), and large-cell carcinoma (1.9%). This frequency reflects the distribution of the histological subtypes of primary lung cancer: adenocarcinoma is the most prevalent one (38.5%), followed by squamous-cell (20%), small-cell (15%), and large-cell carcinoma (3%) (10).
The diagnosis of skin metastasis is usually (64.3% of the cases) made in the setting of a known lung cancer; however, in 34.6% of the cases the skin metastasis is the presenting sign of this cancer.
The survival of patients with cutaneous metastases from lung cancer is usually short, as the patients are in an advanced cancer stage. Skin metastases frequently coexist with metastases to other internal organs. Not surprisingly, most patients die of their disease within a few weeks or months (11).
Surgical resection remains the mainstay curative treatment, especially for early-stage tumours. Most lung cancers are treated with chemotherapy with concurrent radiation and/or immunotherapy (12-14). Surgical removal of skin metastasis can be also considered.
Conclusion
Skin metastases are a rare manifestation of an underlying lung cancer. An early diagnosis by the dermatologist allows prompt management of these patients, even though the prognosis remains poor.
Footnotes
Authors’ Contributions
All Authors contributed to the collection of the data, drafting and preparation of this manuscript. All Authors have read and approved the final version of the manuscript.
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this study.
- Received March 8, 2023.
- Revision received March 17, 2023.
- Accepted March 20, 2023.
- Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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