Background

Small cell lung cancer (SCLC) is a highly aggressive form of pulmonary malignancy which accounts for 15–20% of lung cancer cases [1]. SCLC is well known for its rapid doubling time, tendency to metastasize, and its affinity for relapsing. Nearly 60–70% of patients with SCLC present with disseminated disease [1], and early diagnosis improves outcomes. Typical presentations include cough, dyspnea, and weight loss. However, SCLC can present in more atypical ways.

Paraneoplastic syndromes such as syndrome of inappropriate antidiuretic hormone secretion (SIADH), Lambert-Eaton myasthenic syndrome, hypercalcemia, and Cushing’s syndrome are some atypical presentations. Up to 10% of patients with lung cancer develop a paraneoplastic syndrome during the course of their disease progression [2]. An even smaller number of patients have paraneoplastic syndromes as their presenting feature. It is therefore not surprising that abnormal laboratory values can be misinterpreted as isolated findings when there is no obvious evidence of malignancy.

SCLC has almost an exclusive association with cigarette smoking. In one study, smoking was associated in 100 and 97.9% of cases in men and women, respectively [3]. With this strong of a relationship, SCLC should be considered in current and past smokers with evidence of abnormal laboratories or symptoms consistent with paraneoplastic syndromes. The following case depicts how identifying a paraneoplastic syndrome helped uncover an underlying SCLC and improve one patient’s prognosis.

Case discussion

A 64 year-old caucasian male presented with a chief complaint of nausea and vomiting. These episodes occurred three-to-four times per day for the past 3 days and were non-bilious, non-bloody, mostly foodstuff. There were no precipitating factors or associated symptoms including abdominal pain or diarrhea. He did not complain of any recent pulmonary symptoms such as cough, hemoptysis, dyspnea, or chest pain, and denied any fevers, night sweats, or weight loss. He had no past medical history except for hypercholesterolemia controlled with atorvastatin. His only family history included Hodgkin’s lymphoma. Smoking history revealed 20 pack years and quit 3 months prior to his visit. Vital signs upon presentation were unremarkable. Physical examination revealed mild right upper lung field end-expiratory wheezing, no clubbing of his digits, no jugular venous distention, no lower extremity edema, was euvolemic, and had unremarkable abdominal findings.

An anterior-posterior chest plain film (Fig. 1) was performed in the emergency department, and read by the radiologist as having no evidence of acute cardiopulmonary disease. Laboratories drawn on admission revealed hyponatremia in the context of a low serum osmolality and a high urine osmolality (Table 1). Given these laboratory findings, SIADH ranked high in our differential diagnoses.

Fig. 1
figure 1

Left: AP chest plain film read as no acute cardiopulmonary disease. Right: CT chest showing a conglomeration of nodules and opacities measure 3.0 × 1.9 cm of the inferior portion of the right upper lobe

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Table 1 Blood laboratories from day 1, 2, and 6
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Treatment with fluid restriction was initiated and sodium levels gradually improved (Table 1). The patient’s nausea and vomiting had resolved as his sodium levels improved, which later was attributed to his hyponatremia from SIADH. Potential etiologies for SIADH (i.e. infectious, cerebral, medications, endocrinopathies) were further investigated and were unremarkable. Due to the patient’s significant smoking history, unilateral end-expiratory wheeze, initial poor quality chest imaging, and high-index of suspicion, a CT chest was ordered. It revealed the presence of a conglomeration of nodules and opacities measuring 3.0 × 1.9 cm in the inferior segment of the right upper lobe of the lung with ipsilateral mediastinal lymphadenopathy. Subsequent CT-guided percutaneous biopsy was performed. Biopsy specimen stained positive for CK, CD56, NSE, BcL2, Synaptophysin, PAX-5, and TTF-1, but negative for Chromogranin, CD57, and NFP; consistent with small cell carcinoma. Further metastatic workup including CT abdomen and pelvis along with brain MRI was performed, which showed no evidence of metastasis.

He was subsequently discharged with an appointment with an outside oncologist near his home as he lived far from our institution. A follow-up telephone conversation occurred 4 weeks from discharge. The patient’s oncologist had ordered a whole-body PET scan within 1 week of hospital discharge and it revealed uptake in one ipsilateral mediastinal lymph node. He was classified as having limited stage small cell lung cancer (LS-SCLC) and was undergoing chemotherapy with plans for subsequent prophylactic cranial irradiation. At 4 months follow-up, he had completed three chemotherapy sessions and prophylactic cranial irradiation. His oncologist had deemed him to be in remission and undergoing continued surveillance.

Discussion and conclusions

SCLC can present with three possible manifestations: pulmonary, metastatic, and endocrinologic/neurologic paraneoplastic syndromes. The most common of these three manifestations is metastatic as approximately 70% of patients with SCLC present with metastatic disease [4]. This is a clear testament to the highly aggressive nature of this disease process. For this reason, screening measures have been implemented to help identify SCLC at an earlier stage. Current US Preventive Services Task Force (USPSTF) guidelines recommend screening individuals between 55 and 80 years old with at least a 30 pack year smoking history for lung cancer. The screening modality recommended is a low dose CT scan of the chest. This guideline has been supported by trials such as the national lung screening trial (NLST) which showed a 20% reduction in mortality in patients who met criteria and were screened appropriately.

Unfortunately, as seen in our patient, screening based on age and pack year history alone can lead to missed diagnoses.More recent studies suggest that a screening model using individual risk factors could be superior to the current established guideline. One study investigated the efficacy of nine different screening models based on various risk factors [5]. Risk factors in these screening models included: gender, race, ethnicity, education, body mass index, chronic obstructive pulmonary disease, emphysema, personal history of cancer, personal history of pneumonia, and family history of lung cancer. Results from this study suggest increased sensitivity and specificity for risk factor based screening groups in comparison to NLST guideline based groups. However, both the USPSTF guidelines, and risk factor based screening models have the potential to miss early diagnoses. Our case outlines a patient who does not fit the USPSTF guidelines for screening and does not fit perfectly into any risk factor based screening model.

Therefore, it continues to be a diagnostic challenge to detect early stage lung cancer such as SCLC. The aggressive nature of SCLC leaves physicians with a narrow window for discovering LS-SCLC. Despite advances in screening guidelines and modalities patients often fail to meet criteria and therefore go unnoticed before they present with metastatic disease. Given the possible shortcomings of screening modalities, physicians must rely on their clinical index of suspicion to help discover early disease. This includes a holistic approach to each patient, correlating possible early symptoms of presentation with abnormal lab values that could indicate a possible paraneoplastic syndrome. Identifying these underlying paraneoplastic syndromes may be the key to discovering a LS-SCLC in a patient who otherwise appears asymptomatic. This could significantly alter a patient’s disease course and improve a 5 year survival rate by nearly 45% [5].