Abstract
Background
Superior sulcus tumours (SSTs) are a rare but serious non-small cell lung cancer that requires aggressive multi-modal intervention. Existing literature suggests patient outcomes are adversely affected by diagnosis delay, often from misdiagnosis as a musculoskeletal condition. As such, the aims of this review were to identify the key clinical features of SSTs documented in the literature and differentiate them from commonly misdiagnosed musculoskeletal pathologies.
Methods
In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews (PRISMA-ScR), a systematic search of electronic databases was conducted for studies of SST patients with descriptions of their signs and symptoms. These findings along with information on any length of diagnostic delay or misdiagnosis were extracted for analysis.
Results
The final review included a sample of 1,328 patients across 31 studies. A total of 111 patients had a misdiagnosis resulting in diagnostic delay. The most common presentation across all SSTs was shoulder pain (60.0%), followed by a history of smoking (27.0%), and arm pain (25.6%). Diagnostic delay was most frequently due to radiographic error by primary contact physicians. For patients who received a misdiagnosis, the most common clinical findings were signs and symptoms of upper limb neuropathy (55.7%), shoulder pain (53.2%) and chest pain (27.9%). Within this subgroup, SSTs were most frequently misdiagnosed as cervical spine radiculopathy, cervical spine osteoarthritis, or glenohumeral osteoarthritis. Additionally, within the misdiagnosis subgroup, key features of SSTs such as Horner’s syndrome and history of smoking were less prevalent compared to the larger group.
Conclusions
Explicit testing and differentiation between shoulder and cervical spine pathology are required when examining patients with atraumatic shoulder and/or arm pain to rule out SSTs. Specifically, targeted testing for cervical spine radiculopathy and glenohumeral osteoarthritis can help guide appropriate imaging in the initial stages of assessment. When requested, apical lung imaging should be scrutinized to prevent physicians from missing radiographic signs of SSTs that may lead to diagnostic delay.
Keywords: Superior sulcus tumours (SSTs), Pancoast tumours, misdiagnosis, diagnostic delay, differential diagnosis
Highlight box.
Key findings
• The most frequently documented reasons for superior sulcus tumour misdiagnosis were radiographic errors, diagnosis as shoulder or cervical spine osteoarthritis, or diagnosis as cervical spine radiculopathy.
• Misdiagnosed patients presented with fewer hallmark features of superior sulcus tumours such as Horner’s syndrome and history of smoking.
What is known and what is new?
• Superior sulcus tumours are difficult to treat based on late-stage clinical manifestations and the associated delay in presenting for specialist care.
• Identifying key differentials and excluding them will help primary contact clinicians expedite appropriate imaging and onward referral for superior sulcus tumour patients.
What is the implication, and what should change now?
• When examining patients with atraumatic shoulder and/or arm pain, key red flags should inform primary contact clinicians of the need for imaging for potential superior sulcus tumours. Detailed examination of the lung apex on plain radiography and discrete exclusion of glenohumeral and cervical spine pathology are needed when working with this suspected patient group.
Introduction
Superior sulcus tumours (SSTs) are non-small cell lung cancers (NSCLCs) that manifest at the apex of the lung and invade adjacent ribs, vertebrae and nerves (1). While NSCLCs account for up to 85% of lung cancers, SSTs are somewhat rare and only constitute approximately 5% of NSCLC cases (1). However, SSTs often do not manifest clinically until they reach high-grade tumour staging (IIB and above) (2). As such, they have typically required aggressive trimodality treatment combining surgery, chemotherapy and radiation (3). Even with trimodal intervention, 5-year survival rates are reported at 41% (4). Without trimodal treatment, 5-year survival rates have been reported as low as 20% (5). Given the high level of relative mortality associated with these types of tumours, early identification and intervention is essential for improving patient life expectancy.
One of the confounding factors to early identification of SSTs is the overlap in presentation with several upper limb musculoskeletal pathologies. Given the location of SSTs at the apex of the lung, patients will present with some combination of shoulder and/or arm pain, and brachial plexopathy (6). It has also been reported that respiratory symptoms such as dyspnoea, dry cough, and haemoptysis often do not manifest in SSTs until after musculoskeletal and/or neurological symptoms as they do not initially impact central airways (7). The earlier onset of non-respiratory symptoms has led to reported misdiagnosis as upper quadrant musculoskeletal conditions such as shoulder arthritis, rotator cuff pathology, or cervical spine radiculopathy (8,9). While the presence of Horner’s syndrome (ptosis, miosis and anhidrosis) can help clinicians identify potential SSTs, it is only present in up to 20% of patients (6). These overlapping symptoms have led to reported diagnostic delays of up to 18.5 months for SSTs (10), contributing to the poor prognosis even with appropriate intervention (11). Adding to potential diagnostic delay, the average age of onset for SSTs occurs in the sixth decade of life (12). This overlaps with the age of symptomatic onset for cervical spine osteoarthritis in the fifth to sixth decades (13), and the progressive increase in degenerative shoulder pathology from the sixth decade onwards (14). Given the overlap in both clinical presentation and age of onset, it is imperative primary contact clinicians be able to adequately differentiate between SSTs and common musculoskeletal disorders of the neck and shoulder.
Given the consequences of misdiagnosing SSTs, being able to identify which signs and symptoms best characterise its main differentials is paramount for the primary contact clinician to best direct appropriate diagnostic imaging and referral. As such, the aims of this review were to (I) identify the key features that distinguish SSTs from musculoskeletal conditions; (II) identify the rate and symptomology of misdiagnosis of SSTs; and (III) propose a clinical decision-making algorithm to guide differential diagnosis and medical imaging pathways for suspected SSTs. Given the various research aims, a scoping review methodology was utilised. We present this article in accordance with the PRISMA-ScR reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1969/rc) (15).
Methods
In the first quarter of 2025, four electronic databases (PubMed, Embase, EMCare, and Scopus) were systematically searched using the key terms: (superior sulcus tumour) OR (Pancoast tumour) OR (apical lung tumour) OR (thoracic inlet tumour). All records were extracted to EndNote 20 (16). Eligibility consisted of (I) full-text studies including a cohort of patients with SSTs and (II) studies including patient symptomology or clinical examination findings. Individual case studies were excluded.
Methodological grading and risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist for cohort studies (17). This tool uses 11 questions that are documented as “yes”, “no”, “unclear” or “not applicable”. Given that JBI tool for cohort studies does not have its own scoring system, one was assigned to it by giving a score of “yes” one point and all other responses 0 points. Fractions for each article were then converted to a percentage score to allow equitable comparison among studies. This method has been utilised by other reviews assessing signs and symptoms of neoplasms (18).
Data charting was conducted by extracting and summarizing included studies in tables according to author, year, sample size, study design, patient symptomology, diagnostic delay, and any cause or reason for misdiagnosis inclusive of the alternative pathology. Patient symptomology was recorded as the percentage of the number of patients presenting with the symptom divided by the total number of patients across all studies. The same calculation was done for the symptoms of those who received misdiagnosis or diagnostic delay. No meta-analysis was conducted given the scoping nature of the review and the absence of statistical measures of association reported in the included studies.
Results
The initial search resulted in 4,591 results, of which 2,378 were screened after the removal of duplicates and ineligible records. A total of 25 articles were included after application of the inclusion criteria (Figure 1). Screening of the reference lists for these articles identified another six articles for inclusion, resulting in a total of 31 studies for the final review.
Figure 1.
PRISMA-ScR flow diagram.
Of the 31 studies included, there were four prospective cohort studies (19-22) pre-2015 and one post-2015 (23). There were 25 retrospective cohort studies pre-2015 (8,9,24-46) and one post-2015 (47). Individual references and study details including sample size and methodological scoring are outlined in Table 1.
Table 1. Study characteristics and methodological grading.
| Study | Year | Study design | Sample size | JBI score |
|---|---|---|---|---|
| Abdelrahman et al. (24) | 2010 | Retrospective cohort | 23 | 73% |
| Attar et al. (25) | 1979 | Retrospective cohort | 73 | 73% |
| Attar et al. (26) | 1998 | Retrospective cohort | 105 | 91% |
| Deng et al. (9) | 2011 | Retrospective cohort | 26 | 55% |
| Favaretto et al. (19) | 2010 | Prospective cohort | 38 | 82% |
| Fridriksson et al. (27) | 2015 | Retrospective cohort | 12 | 36% |
| Fuller and Chambers (28) | 1994 | Retrospective cohort | 24 | 73% |
| Gu et al. (8) | 2012 | Retrospective cohort | 10 | 36% |
| Herbert et al. (29) | 1992 | Retrospective cohort | 30 | 82% |
| Ichiki et al. (30) | 2013 | Retrospective cohort | 50 | 55% |
| Ichinohe et al. (31) | 2006 | Retrospective cohort | 50 | 73% |
| Jeannin et al. (32) | 2015 | Retrospective cohort | 36 | 91% |
| Kappers et al. (33) | 2008 | Retrospective cohort | 52 | 82% |
| Kocak et al. (34) | 2011 | Retrospective cohort | 33 | 82% |
| Kunitoh et al. (20) | 2008 | Prospective cohort | 76 | 91% |
| Marra et al. (21) | 2007 | Prospective cohort | 31 | 82% |
| Maggi et al. (22) | 1994 | Prospective cohort | 72 | 55% |
| Martinod et al. (35) | 2002 | Retrospective cohort | 139 | 73% |
| Marulli et al. (36) | 2015 | Retrospective cohort | 56 | 73% |
| Miller et al. (37) | 1979 | Retrospective cohort | 26 | 45% |
| Moon et al. (38) | 2011 | Retrospective cohort | 24 | 91% |
| Ozmen et al. (39) | 2015 | Retrospective cohort | 47 | 82% |
| Rzyman et al. (47) | 2023 | Retrospective cohort | 47 | 91% |
| Sartori et al. (40) | 1992 | Retrospective cohort | 42 | 73% |
| Shahian et al. (41) | 1987 | Retrospective cohort | 18 | 55% |
| Stanford et al. (42) | 1980 | Retrospective cohort | 53 | 73% |
| Strojan et al. (43) | 1997 | Retrospective cohort | 48 | 45% |
| Truntzer et al. (44) | 2014 | Retrospective cohort | 42 | 91% |
| Villas et al. (45) | 2004 | Retrospective cohort | 10 | 36% |
| Weykamp et al. (23) | 2024 | Prospective cohort | 14 | 91% |
| Wright et al. (46) | 1987 | Retrospective cohort | 21 | 45% |
JBI, Joanna Briggs Institute.
In total, 1,328 patients had clinical signs and symptoms documented across the 31 included studies. Five studies reported on SST misdiagnosis and/or specific diagnostic delays (8,9,24,31,45), resulting in a cohort of 111 patients for subgroup analysis of symptomology. Where specific misdiagnosis and diagnostic delay were reported, they are presented in Table 2.
Table 2. Misdiagnosis types, prevalence, and delays for superior sulcus tumours.
| Study | Misdiagnosis | Diagnostic delay (months) |
|---|---|---|
| Abdelrahman et al., 2010 (24) | Shoulder bursitis (n = unknown) | Range, 3.0–9.0 (mean: 5.0) |
| Shoulder osteoarthritis (n = unknown) | ||
| Cervical spine radiculopathy (n = unknown) | ||
| Deng et al., 2011 (9) | Shoulder osteoarthritis (n=13) | – |
| Cervical spine osteoarthritis (n=3) | ||
| Pulmonary tuberculosis (n=3) | ||
| Gu et al., 2012 (8) | Cervical spine radiculopathy (n=10) | Mean: 2.7 |
| Ichinohe et al., 2006 (31)† | Lesion missed on imaging (n=78) | Range, 1.3–13.3 (mean: 4.8) |
| Lesion misdiagnosed on imaging (n=20) | ||
| Villas et al., 2004 (45) | Cervical spine osteoarthritis (n=1) | Range, 3.0–24.0 (mean: 13.0) |
| Cervical spine radiculopathy (n=1) | ||
| Scapulothoracic pain (n=1) | ||
| Brucellosis (n=1) | ||
| Pancreatitis (n=1) |
†, study evaluated 166 radiographs among a sample of 50 patients.
The most frequently reported symptom for SSTs was shoulder pain, which was present in 60% of all patients. Following this, upper limb neuropathic signs of conduction loss were present in 27.6% of patients. Specific levels of neuropathic symptoms are listed in Figure 2, with T1 neuropathy being the most common at 9.5%. The third most common feature was a history of smoking which was noted in 27% of patients, followed closely by arm pain which was reported in 25.6%. Various amounts of unexplained weight loss were reported in 20.3% of patients, with 13.4% of patients reporting weight loss of <5% body weight. Horner’s syndrome was noted in 17.5% of the total sample. All other symptoms accounted for <6% of patient presentations.
Figure 2.
Symptomology of patients with superior sulcus tumours (n=1,328).
Among patients that had diagnostic delay or received a misdiagnosis, the most prevalent symptom was upper limb neuropathy with conduction loss which was present in 57%. The second most prevalent symptom in this group was shoulder pain at 53.2%. Chest pain, thoracic back pain and arm pain account for 27.9%, 26.1%, and 21.6% of symptoms, respectively. A history of smoking was noted in 19.8% of patients, and cough in 14.4%. All other features in misdiagnosed subgroup accounted for <10% of symptomology (Figure 3).
Figure 3.
Symptomology of misdiagnosed superior sulcus tumours patients (n=111).
Discussion
This scoping review aimed to differentiate the clinical features of patients presenting with SSTs who were initially misdiagnosed or underwent notable diagnostic delay compared to the broader population of patients with SSTs. We reviewed 31 studies, 5 of which reported data on misdiagnosis types, rates and diagnostic delay. Of the included 1,328 patients in this review, 111 (8.3%) had diagnostic delay or received misdiagnosis. The most documented reason for diagnostic delay was misinterpretation of radiography, followed by misdiagnosis as a musculoskeletal condition of the cervical spine or shoulder.
Diagnostic delays were reported in four studies and ranged from 1.3 months (31) to 24 months (45), with the longest average delay being 13.0 months (45). The most frequently reported cause of diagnostic delay was radiographic error by the reviewing physician either missing the lesion entirely, or diagnosing it as non-malignant (31). This resulted in tumour stage progression and metastasis in 22 out of 40 patients. This same study also reported that patients visited between one and four physicians before receiving a correct diagnosis, with 46% of patients initially presenting to a general practitioner or orthopaedist, and another 13% of patients being treated by physiotherapists for up to 2 months without improvement. This underscores the importance of primary contact clinicians and orthopaedists being aware of the potential of SSTs when examining patients with upper quadrant pain, especially when symptoms are recalcitrant or not responding as expected to intervention. Although this review could not directly quantify the impact of diagnostic delay on survival, existing literature suggests that delays often lead to stage progression, which is a major determinant of prognosis. Meta-analytic evidence indicates that lower tumour and lymph node stages are strongly associated with improved survival, whereas advanced stages significantly worsen outcomes (48). Given that diagnostic delay frequently results in higher staging and reduced resectability, early detection remains critical for optimizing treatment success and long-term survival.
While the sensitivity of plain radiography for detecting lung cancers has been reported up to 80% (49), it doesn’t factor in the difficulties associated with imaging the apical section of the lung. To address this, previous reviews have suggested using lordotic views on radiographs, and carefully examining for pleural thickening at the apex of the lung with or without destruction of adjacent ribs and vertebrae (12). In contrast, however, one cohort study reported successful diagnosis by orthopaedists by examining AP radiographs of the cervical spine and detecting separation of pulmonary air from the first rib (45). While computed tomography (CT) scans are preferred over X-ray and have utility for tumour staging, the use of magnetic resonance imaging (MRI) would be considered the imaging modality of choice for SSTs with reported diagnostic sensitivity of 90% and specificity up to 86% (50,51). However, it is important to acknowledge that not all primary contact clinicians may have MRI access, which places a higher degree of reliance on patient history, physical examination and clinical reasoning.
Misdiagnosis as a musculoskeletal pathology was the second most common reason for diagnostic delay for SST patients. The most common misdiagnoses were cervical spine radiculopathy (8,24,45), cervical spine osteoarthritis (9,45), and shoulder osteoarthritis (9,24). This overlaps with the most prominent symptoms from this review, as the most common feature of SSTs was shoulder pain, which was present in 60.0% of all cases. It was also the second most prevalent symptom in the misdiagnosis group, presenting in 53.2% of patients. While shoulder pain can have a broad number of medical differentials, the most common misdiagnosis from clinicians in this review was glenohumeral osteoarthritis. This is potentially due to the commonality of shoulder pain and overlap in age of onset, however it was not explicitly elaborated on in cohorts noting misdiagnosis. In cases where misdiagnosis or diagnostic delay was reported, upper limb neuropathic findings of conduction loss were the most common clinical finding presenting in 57.0% of patients. However, only 27.6% of all SST cases were reported to have neuropathic symptoms of conduction loss. The higher prevalence of upper limb neurological symptoms in the misdiagnosis group matches the notable amount of incorrect differentials as cervical radiculopathy or osteoarthritis, both of which commonly refer pain to the shoulder, arm, and hand and can present with compressive neuropraxia (52,53). It is noted, however, that the definition of neuropathy and neuropathic symptoms was not well standardized throughout many of the articles. Additionally, Horner’s syndrome was reported far less often in the misdiagnosed group (5.4% versus 17.5% in all patients) which may draw suspicion away from SSTs given that it is considered a hallmark feature of the pathology (30). History of smoking also presented less frequently in the misdiagnosis group, appearing in 19.8% of patients as opposed to 27% of the total group. Overall, the number of symptoms that could be related to cervical spine or shoulder pathology was more prevalent in the misdiagnosis group, and the cornerstone features of SSTs such as Horner’s syndrome and smoking history were less frequent. This shift in symptomology could lead practitioners away from SST suspicion and matches the corresponding musculoskeletal misdiagnosis rates from this review.
To improve clinical recognition of SSTs, first contact clinicians should prioritise several key information sources from the patient history and objective examination with the goal of reducing the likelihood of misdiagnosis and guiding decision making regarding the need for medical imaging (Figure 4). In the patient with shoulder pain that has Horner’s syndrome, and a history of smoking and/or weight loss, apical lung imaging should be included due to the high clinical suspicion of SST. In the absence of these findings, glenohumeral joint crepitus has a reported sensitivity and specificity of 75% and 60%, respectively, in the diagnosis of glenohumeral osteoarthritis (54). Additionally, a loss of passive external rotation range of motion has a reported specificity of 80% for glenohumeral osteoarthritis, but a sensitivity of less than 50% (54). SSTs do not present with mechanical shoulder pain associated with movement, and this should be examined discretely by the clinician when attempting to rule in local musculoskeletal pathology of the shoulder. If radicular-like symptoms are present distal to the cervical spine, Spurling’s test has a reported sensitivity of 90–100% and specificity of 94–100% for the diagnosis of cervical spine radiculopathy (55). The test itself is a provocative manoeuvre used to assess cervical radiculopathy. It involves extending and rotating the patient’s neck toward the symptomatic side while applying axial compression. A positive test reproduces radicular pain in the arm, suggesting nerve root involvement. This same study also noted a specificity of 90–97% for cervical radiculopathy with cervical traction/distraction testing, though with a much lower sensitivity (44%). If both tests are positive in patients with shoulder or distal arm pain, it would strongly imply the cervical spine as a generator of distal pain and/or neurological conduction loss.
Figure 4.
Clinical examination flowchart for suspected superior sulcus tumours. CT, computed tomography; ER, external rotation; GHJ, glenohumeral joint; MRI, magnetic resonance imaging.
The main limitations of this review revolve around the methodology of the included studies. The retrospective nature of most of the included studies resulted in inconsistent reporting of diagnostic delay. Only four of the 31 studies provided explicit data on delay duration, and definitions of diagnostic delay were not standardized across studies. This variability limits the ability to perform meta-analysis and may introduce bias when interpreting the frequency and impact of delayed diagnosis. Future research should aim to adopt uniform definitions and prospective designs to better quantify diagnostic timelines. Additionally, the inclusion of SST signs and symptoms was not always standardised which limits the strength of the conclusions that could be made from this review. This review spans several decades, and the inclusion of older studies was necessary due to the rarity of SSTs and the limited number of cases reported in recent years. Importantly, recent cohorts (23,30,47) continue to document diagnostic delays and misdiagnosis patterns similar to those observed historically, suggesting that these challenges persist despite advances in imaging and multidisciplinary care. Nonetheless, we acknowledge that improvements in diagnostic technology and clinician awareness may have reduced the overall frequency of delays, and this temporal variability represents a limitation of the review.
Conclusions
While the presence of SSTs is low in the general population, there is high risk of early mortality for those with misdiagnosis. When suspected, careful interpretation of apical view radiographs is essential if MRI is not an immediate option for clinicians, with a high suspicion being directed towards any pleural thickening at the apex of the lung. Explicit and targeted testing of the shoulder and neck to rule out osteoarthritis and cervical spine radiculopathy can help primary contact clinicians direct suspicion towards SSTs. This is especially paramount when patients present without overt red flags of lung cancer such as smoking history or weight loss, or without hallmark features of SST such as Horner’s syndrome.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Footnotes
Reporting Checklist: The authors have completed the PRISMA-ScR checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1969/rc
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1969/coif). The authors have no conflicts of interest to declare.
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