Smoker’s Painless Skin Nodules Flag a Fatal Diagnosis

An 87-year-old white man presented to a hospital emergency surgical department with two round, grayish-brown nodules on his abdomen. He reported having felt tired and dizzy for the last few months. However, he had not experienced any weight loss. He had a 120 pack-year history of tobacco use. He was not taking any medications and told clinicians that he had not experienced a cough, chest pain, shortness of breath, or other breathing problems.

Clinicians noted that the man appeared to be in good health and state of nutrition for his age, with a BMI of 20.5. On initial assessment, clinicians found his skin nodules were painless, clearly visualized, and mobile (not fixed in the skin). One nodule located on the left lumbar region was 4 cm by 5 cm in size (Figure), while the other was on the right iliac region and measured 3.5 cm by 2 cm. Physical examination also detected several swollen lymph nodes on both sides of his neck and enlargement of single nodes in the right armpit and right groin.

The man’s blood pressure was 140/90 mm Hg, his body temperature was 36.7°C, and his oxygen saturation level was 95%.

When he was admitted to the surgical department, results of his blood and serum examinations were within normal range with a few exceptions: carcinoembryonic antigen (274.5 ng/mL), cancer antigen 15-3 (14.56 U/mL), neuron-specific enolase (48.84 ng/mL), amylase (104 U/mL), and alkaline phosphatase (152 U/L).

A chest X-ray revealed a number of nodular lesions in the lower lobe of his right lung and pleural effusion in both lungs. On the day the patient was admitted to the hospital, clinicians performed surgery to excise the skin lesions for biopsy and requested immediate histological examination of the lesions.

A subsequent CT scan confirmed findings of the chest X-ray and also showed spleen and right adrenal gland induction, along with multiple nodes in the brain. The CT scan also revealed multiple subcutaneous nodular lesions in the abdominal region. Imaging did not reveal any foci in the liver or in the bone.

About 48 hours later, the histology report confirmed the skin lesions to be metastatic small cell lung cancer (SCLC). On day 7 in hospital, the patient received an initial cycle of IV chemotherapy with cisplatin and etoposide, with clinicians prepared to provide palliative radiation therapy if the lesions bled or became painful.

On day 12, the patient’s clinical condition declined dramatically, and he lost consciousness. He received appropriate supportive and cerebral decompressive treatment with dexamethasone at 4 mg by IV thrice daily, because his condition did not allow complete treatment with full chemotherapy and radiation.

On day 50 after being admitted to hospital, the patient died in the ICU.

Discussion

Clinicians reporting this case of an 87-year-old patient with a history of smoking who presents with two nodules in the skin of the abdomen noted that, while rare, SCLC can metastasize to the skin. They urged a high level of suspicion of metastatic disease when patients (particularly the elderly) present with atypical skin lesions, regardless of the patient’s smoking history.

As the most aggressive form of lung cancer, SCLC causes 13% of lung cancer diagnoses worldwide, authors wrote. The tumor location is used to classify the carcinoma as limited-stage for the 30% of newly-diagnosed tumors in the hemithorax of origin, the mediastinum, or the supraclavicular lymph, the group explained. Conversely, extensive-stage disease involves tumors that have spread beyond the supraclavicular areas.

Everyday medical practice suggests that in many cases, lung cancer, especially SCLC, is a systemic disease, authors noted. Metastases of SCLC beyond the lungs are often observed, “even in patients with apparently restricted lung tumors, and these patients are often dying from systemic metastases,” they wrote. SCLC, which is generally noted to grow quickly and spread early, has been referred to in recent years as grade IV pulmonary neuroendocrine carcinoma, the case report authors noted.

In patients with limited SCLC, therapeutic curative efforts include combined chemotherapy and radiotherapy, which is associated with median survival of 23 months and 5-year survival rates of 12% to 17%. In cases of extensive disease, usual treatment with chemotherapy has a median survival ranging from about 7 to 12 months, authors noted, with only 2% of patients surviving to 5 years.

In addition to smoking, the group listed a variety of lung cancer risk factors, including exposure to industrial compounds such as asbestos, arsenic and chromium, residential radon, vapors from cooking oil, indoor coal, and wood burning. The group also suggested that infection with human papillomavirus 16 and 18 may have a causative role, although data on this potential etiology are mixed.

The likelihood of developing lung cancer is also increased by as much as 13% in people with pre-existing lung disease who have never used tobacco, with the risk of small cell carcinoma particularly low, authors wrote. However, they cautioned that for nonsmokers who live with smokers, the risk of lung cancer exceeds 24%.

SCLC is difficult to identify, especially at early stages, in which signs and symptoms do not appear. Thus, cancer can spread to other sites, even before the primary occurrence is diagnosed. For instance, patients experiencing cancer in advanced stages may be entirely unaware of their disease and may be diagnosed only after undergoing a CT scan for an unrelated condition.

Skin metastases have been observed in up to 12% of lung cancer patients and, along with soft tissue metastases, affect approximately 8% of patients dying of lung cancer, the group wrote. SCLC specifically tends to metastasize to the brain, liver, adrenal glands, bone, and bone marrow, while – unlike other histological types of lung cancer – metastases to the skin are rare and usually present at an advanced stage. Less commonly, cutaneous metastases “may be concurrent with the diagnosis and may also present as the first sign of the illness,” the group noted.

“Lesions present as painless subcutaneous or intramuscular masses, often nodular, mobile or adherent, hard or flexible, oval or round, single or multiple, and varied in size,” they added. Less commonly, lung cancer metastases present as ulcerations or sclerodermoids, they noted, or as “plaque-like lesions, erysipelas-like papules, and zosteriform lesions [which] may mimic local infection.”

Because there is no typical presentation for lung cancer-to-skin metastases, these skin lesions cannot be distinguished from dermal metastases generated by cancers in other organs, case authors noted: “Differential diagnosis also includes squamous cell carcinoma, basal-cell carcinoma, amelanotic melanoma and Merkel cell carcinoma. Diagnosis is by biopsy.”

A retrospective study of cutaneous metastases of various cancers in 381 patients found that 33.6% had cutaneous infiltrative lesions present at diagnosis of the primary tumor.

Case report authors noted that skin metastases can occur with all histological types of lung cancer, although it is more common with adenocarcinoma and large cell carcinoma, and comparatively rare with squamous cell and small cell carcinoma. They cited series reporting that cutaneous lesions represent a first sign of malignancy in 7% to 24% of lung cancer patients.

According to a retrospective Spanish study of 30 patients (29 men) diagnosed with skin metastases from various types of lung carcinoma between 1988 and 2009, cutaneous metastases were present (often located on the head) at the time of diagnosis of the lung primary tumour in 66% of cases.

There are various data on the incidence of metastases in the skin. Some reports ranked lung cancer first among malignant sources in men (24%) and fourth in women (4%), following breast cancer, colorectal cancer, melanoma, and ovarian cancer.

Other authors suggested that “breast cancer is the most common form of cutaneous metastasis in women because of its high prevalence rate, [while] lung cancer is the most common primary malignancy to metastasize to the skin in men…The second most common primary source of metastatic skin disease involving both sexes is colorectal carcinoma.”

Untreated SCLC “has the most aggressive clinical course of any type of pulmonary tumor, with a median survival from diagnosis of only 2 to 4 months,” case authors wrote. Citing 2021 statistics from the American Cancer society, they noted that “more than 95% of all SCLC cases transcend Stage I, and there is no benefit from surgical resection for advanced-stage disease.”

However, solitary lesions can be managed surgically with excision combined with chemotherapy, radiation, or both, they noted, adding that chemotherapy alone is preferable in patients with multiple skin metastases, especially if they are bleeding or painful. In general, authors noted that metastasis to the skin is associated with a poor prognosis. Other factors linked with a poor outcome, in which treatment is only palliative, include non-resectable primary SCLC, multiple cutaneous metastases, and presence of other distant metastases.

The case report authors added that immunotherapy, such as with atezolizumab (Tecentriq) and durvalumab (Imfinzi), has also shown promise for advanced SCLC disease and, when combined with chemotherapy as the first-line treatment, “seems to help some people live longer.”

The group noted that because lung cancer is typically asymptomatic in its early stages, the American Association for Thoracic Surgery recommends annual chest screening, including use of low-dose CT screening for those at higher risk.

Case authors concluded by urging use of annual chest screening with low-dose CT in high-risk patients, since patients with lung cancer can be asymptomatic. Additionally, they emphasized the value of smoking-prevention programs and control of occupational exposure to culprit substances, given the high mortality associated with SCLC and limited advances in therapy.