Marked Leukocytosis and Subclavian Vein Occlusion from Pancoast Tumor Mimicking Cellulitis: A Case Report

Abstract

Introduction

Lung cancer can present with atypical clinical manifestations that may mimic benign conditions. We report an extremely rare case of lung cancer initially misdiagnosed as cellulitis due to unilateral upper limb swelling and elevated inflammatory markers.

Case Presentation

A 65-year-old woman with a history of heavy smoking presented with progressive swelling and pain in the left upper limb, accompanied by leukocytosis and elevated inflammatory markers. She was initially diagnosed with cellulitis and treated with antibiotics without improvement. Contrast-enhanced computed tomography revealed a left apical lung tumor invading the chest wall and occluding the subclavian vein. Histopathological examination confirmed primary non-small-cell lung carcinoma, favoring adenocarcinoma. The patient also exhibited tumor-associated extreme leukocytosis and experienced rapid disease progression despite supportive care, dying 37 days after admission.

Discussion

This case illustrates the diagnostic challenges posed by lung cancer presenting with atypical, infection-like manifestations. Pancoast tumors involving the subclavian vein can cause upper limb edema, while tumor-associated leukocytosis can mimic inflammatory responses. Because extreme leukocytosis in solid tumors is associated with poor prognosis, early recognition is crucial.

Conclusion

Even when clinical findings suggest infection, malignancy should be considered in the differential diagnosis, particularly in patients with risk factors such as smoking or advanced age. Prompt chest imaging is essential to avoid diagnostic delay in such cases.

Introduction

Lung cancer is one of the leading causes of cancer-related mortality worldwide and is associated with a wide spectrum of clinical manifestations [1, 2]. Although respiratory symptoms such as cough, hemoptysis, chest pain, and dyspnea are common, a subset of patients may present with nonspecific manifestations. In such cases, diagnosis is frequently delayed, increasing the risk of misdiagnosis and inappropriate clinical management. Pancoast tumor (also known as superior sulcus tumor) is a distinct lung cancer subtype that originates in the lung apex and frequently infiltrates the chest wall or adjacent neurovascular structures. Its characteristic clinical features include shoulder pain radiating to the upper limb, ipsilateral upper limb edema, and Horner syndrome [3, 4]. However, these symptoms overlap with those of musculoskeletal disorders and infectious conditions, which often leads to delayed diagnosis. Furthermore, tumor-associated leukocytosis (TAL) is a paraneoplastic phenomenon that may closely resemble infection-related inflammatory responses, further obscuring the underlying diagnosis [5, 6]. Cases in which these pathologies coexist are extremely rare.

We report a case of lung cancer presenting with left upper limb swelling and elevated inflammatory markers that was initially diagnosed as cellulitis. Subsequent evaluation revealed a Pancoast tumor causing subclavian vein obstruction, accompanied by TAL. This case is diagnostically and clinically significant because it represents an atypical presentation of lung cancer that mimicked an infectious disease.

Case Presentation

A 65-year-old woman with a history of hypothyroidism, well controlled with oral levothyroxine sodium, presented with progressive left shoulder pain that had persisted for 6 months. She had no history of malignancy and reported a long-standing smoking history of 40 cigarettes per day since the age of 18. Her body mass index was 21.7 kg/m², and she was a homemaker. Four days before presentation, she developed swelling of the left upper limb, and she sought medical attention because of worsening pain. She reported that progressive difficulty in elevating her left arm was interfering with her daily activities. She denied any history of trauma, skin trauma, itching, insect bites, or other potential sources of infection.

Physical examination revealed diffuse swelling of the left upper limb extending from the dorsum of the hand to the upper arm, accompanied by erythema over the forearm. The swelling was more pronounced distally, and the pain was localized to the left shoulder and upper arm (shown in Fig. 1). Vital signs were within normal limits. Laboratory results were as follows: aspartate aminotransferase 18 U/L, alanine aminotransferase 15 U/L, lactate dehydrogenase 451 U/L, alkaline phosphatase 169 U/L, cholinesterase 129 U/L, albumin 1.9 g/dL, C-reactive protein (CRP) 10.6 mg/dL, white blood cell (WBC) count 14,200/µL (neutrophils 82.6%), hemoglobin 11.2 g/dL, platelet count 39.5 × 10⁴/µL, erythrocyte sedimentation rate 85 mm, activated partial thromboplastin time 27.4 s, prothrombin time-international normalized ratio 1.12, fibrin degradation products 11.1 µg/mL, and D-dimer 6.3 µg/mL. Cellulitis was suspected, and intravenous cefazolin followed by oral cefaclor was initiated.

Fig. 1.

Photograph of the left upper limb demonstrating diffuse swelling, more pronounced distally, with associated forearm erythema.

At the follow-up visit 3 days later, CRP level had increased to 15.0 mg/dL, and the WBC count had risen to 18,700/µL (neutrophils 79.9%), indicating worsening inflammation. Other laboratory parameters remained stable, and no clinical improvement was observed despite oral antibiotic therapy. Hospitalization was recommended; however, the patient declined admission and continued outpatient management.

On day 8, she presented to the emergency department with impaired mobility. Her vital signs on arrival were as follows: temperature 38.5°C, blood pressure 116/78 mm Hg, pulse 110 beats/min, respiratory rate 15 breaths/min, and peripheral oxygen saturation 98% (on 5 L/min oxygen). Laboratory evaluation revealed further elevation of inflammatory markers (CRP 19.3 mg/dL, WBC count 22,700/µL [neutrophils 83.7%], procalcitonin 0.20 ng/mL, activated partial thromboplastin time 28.8 s, prothrombin time-international normalized ratio 1.20, fibrin degradation product 8.0 µg/mL, and D-dimer 4.3 µg/mL).

Contrast-enhanced computed tomography revealed a 13.3-cm mass extending from the left lung apex beyond the first to third ribs and infiltrating the chest wall, with associated rib destruction (shown in Fig. 2a, b). The tumor protruded anterolaterally and had encased and occluded the left subclavian vein. A left-sided pleural effusion was present. The left subclavian artery traversed the tumor, showing luminal narrowing without occlusion. In addition, enlarged cervical, axillary, and mediastinal lymph nodes were identified, along with right adrenal gland enlargement, findings suggestive of metastatic disease. The tumor location and extent explained the patient’s clinical symptoms, including progressive shoulder pain due to chest wall and possible brachial plexus involvement, and left upper limb swelling caused by venous congestion secondary to subclavian vein occlusion. The lack of clinical response to antibiotic therapy and imaging findings demonstrating subclavian vein occlusion and an apical lung mass suggested a tumor-related rather than infectious etiology.

Fig. 2.

Contrast-enhanced chest CT and brain magnetic resonance imaging findings. a Axial contrast-enhanced CT image demonstrating occlusion of the left subclavian vein (red arrow). b Axial contrast-enhanced CT image showing a large apical lung mass protruding anterolaterally beyond the first to third ribs with associated rib destruction. c Gadolinium-enhanced brain magnetic resonance imaging showing metastatic lesions in the cerebral hemispheres; two lesions are visible in this image. d Serial chest CT images demonstrating progressive tumor enlargement by day. CT, computed tomography.

The patient was admitted for further evaluation. A needle biopsy of the left anterior chest wall mass revealed large tumor cells arranged in solid sheets with areas of necrosis and prominent neutrophilic infiltration. Immunohistochemical analysis demonstrated thyroid transcription factor 1 positivity in approximately 10% of tumor cells, consistent with adenocarcinoma, whereas staining for napsin A, p40, cytokeratin 5/6, cluster of differentiation 56, synaptophysin, and chromogranin A was negative. Based on these findings, the lesion was diagnosed as primary non-small-cell lung carcinoma, favoring adenocarcinoma (shown in Fig. 3). The presence of both mononuclear and multinucleated giant cells suggested possible pleomorphic carcinoma. However, the limited volume of biopsy tissue precluded a definitive histopathological classification. Molecular testing revealed no detectable driver gene mutations, and PD-L1 expression was negative. These pathological and immunohistochemical findings were crucial in establishing the diagnosis of primary non-small-cell lung carcinoma.

Fig. 3.

Histopathological findings of the needle biopsy specimen. a Hematoxylin and eosin staining (×200) showing large tumor cells arranged in solid sheets with areas of necrosis and prominent neutrophilic infiltration. b Immunohistochemical staining for TTF-1 (×200) demonstrating focal positivity, supporting adenocarcinoma differentiation. TTF-1, thyroid transcription factor 1.

Gadolinium-enhanced brain magnetic resonance imaging revealed three metastatic lesions (shown in Fig. 2c). Serum tumor marker levels were as follows: carcinoembryonic antigen <0.3 ng/mL, squamous cell carcinoma antigen 2.1 ng/mL, pro-gastrin-releasing peptide 60.4 pg/mL, cytokeratin 19 fragment 16.1 ng/mL, neuron-specific enolase 19.7 ng/mL, and sialyl Lewis X antigen 47.3 U/mL. Based on these findings, the disease was classified as stage IVB lung cancer (T4N2M1c). Systemic chemotherapy was considered; however, it was not administered because of the patient’s poor general condition (performance status 4) and her preference for best supportive care.

Computed tomography performed on day 20 demonstrated marked tumor enlargement (shown in Fig. 2d). Subsequently, both CRP and WBC levels continued to rise, reaching 17.7 mg/dL and WBC 66,600/µL (neutrophils 96%), respectively, on day 45. The procalcitonin level was markedly elevated at 26.1 ng/mL. Tumor marker levels on the same day were carcinoembryonic antigen 0.5 ng/mL, squamous cell carcinoma 8.1 ng/mL, pro-gastrin-releasing peptide 76.5 pg/mL, cytokeratin 19 fragment 79.9 ng/mL, and neuron-specific enolase 23.5 ng/mL. Despite supportive care, rapid tumor progression led to progressive clinical deterioration, and the patient died of respiratory failure on day 47.

Discussion

The present case initially presented with unilateral upper limb swelling, pain, and markedly elevated inflammatory markers, leading to an initial diagnosis of cellulitis. Subsequent diagnostic evaluation, however, revealed an underlying lung malignancy. Lung cancer is known for its heterogeneous clinical presentations and may mimic a wide range of nonmalignant conditions, resulting in diagnostic delay [1, 2]. To date, reports of lung cancer initially misdiagnosed as upper limb cellulitis remain rare.

In this patient, unilateral upper limb swelling and elevated inflammatory markers were ultimately attributed to edema secondary to compression and obstruction of the left subclavian vein due to lung cancer, concurrent with an inflammatory response caused by TAL. The simultaneous presence of venous obstruction and TAL contributed to a clinical presentation that closely resembled cellulitis.

Occlusion of the subclavian vein is a recognized feature of the so-called Pancoast-Tobias syndrome. A Pancoast tumor arises from the apical region of the lung and invades adjacent chest wall or neurovascular structures, producing a constellation of characteristic clinical manifestations collectively termed Pancoast-Tobias syndrome [3, 4]. This syndrome is classically defined by one or more of the following features [1]: progressive shoulder pain radiating to the neck, axilla, anterior chest, and medial aspect of the arm and forearm due to invasion of the chest wall or brachial plexus [2]; Horner syndrome, characterized by ipsilateral ptosis, miosis, enophthalmos, and anhidrosis resulting from invasion of the sympathetic chain or stellate ganglion [3]; weakness and atrophy of hand muscles caused by ulnar nerve involvement [4]; and upper limb edema secondary to infiltration or obstruction of the subclavian vein. Our patient had upper limb edema, but this symptom was initially attributed to an infectious process. Previous reports have described cases in which upper limb pain associated with Pancoast-Tobias syndrome led to misdiagnosis as other diseases [7–9]. Because the symptoms of Pancoast tumors are often nonspecific and overlap with those of other musculoskeletal or infectious disorders, the possibility of a malignant tumor invading the thoracic inlet should always be considered in patients presenting with such symptoms.

This case was also notable for the presence of TAL. Initially, the left upper limb swelling and markedly elevated inflammatory markers led to a diagnosis of infection. Subsequent evaluation demonstrated that the leukocytosis was tumor-related rather than infectious in origin. Notably, this patient developed extreme leukocytosis. In patients with solid tumors, extreme leukocytosis is commonly defined as a WBC count exceeding 40,000–50,000/μL [10] and has been reported across nearly all types of solid malignancies [5]. TAL is generally associated with a poor prognosis, with approximately 76% of patients dying within 12 weeks of onset [5, 6]. In contrast, patients who survived for more than 1 year in prior studies typically underwent aggressive chemotherapy or surgical intervention [5]. In the present case, both WBC and neutrophil counts increased progressively over the clinical course. Jayarangaiah et al. [11] similarly reported that a progressive rise in WBC and neutrophil levels was associated with poor prognosis. Consistent with these observations, our patient exhibited rapid tumor enlargement over a short period, reflecting a highly aggressive disease course. Therefore, early recognition and therapeutic intervention are essential, as delayed diagnosis can worsen prognosis. Tumor-associated inflammatory responses may closely mimic infection or other inflammatory conditions, particularly when accompanied by localized swelling and erythema, as observed in this case. Differentiating TAL from infection is therefore challenging but critical for appropriate management. Consequently, when evaluating patients with elevated inflammatory markers, clinicians should consider leukocytosis secondary to malignancy as part of the differential diagnosis.

This case illustrates an atypical presentation of lung cancer. The principal lesson is that in patients with risk factors such as a history of smoking, prior malignancy, or advanced age, lung cancer should be carefully considered even when symptoms are nonspecific. Presentations that appear consistent with benign conditions, including infection, may obscure an underlying malignancy. Clinicians should therefore maintain a high index of suspicion and include cancer in the differential diagnosis when clinical features are atypical or refractory to standard treatment. During the initial evaluation, careful assessment of smoking history and early chest imaging in selected patients is essential to prevent diagnostic delays.

Conclusion

This case report describes a rare presentation of lung cancer in which subclavian vein obstruction caused by a Pancoast tumor and TAL occurred concurrently, leading to an initial misdiagnosis of cellulitis. Although swelling accompanied by elevated inflammatory markers is commonly attributed to infection, such findings are not invariably infectious in origin, and malignant etiologies should also be considered in the differential diagnosis. In patients with risk factors such as a history of smoking or advanced age who present with nonspecific symptoms, the possibility of lung cancer should be carefully evaluated. Early chest imaging is essential to prevent diagnostic delays.

Statement of Ethics

Ethical approval was not required for this case report, as per the policies of our Institution’s Ethics Committee. Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent for publication of the case details and accompanying images was obtained from the patient. The CARE Checklist has been completed by the authors for this case report and is provided as supplementary material (for all online suppl. material, see https://doi.org/10.1159/000551217).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The researchers did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author Contributions

Hiroshi Shintani contributed to the concept, drafting of the work, approved the final version to be published, and agreed to be accountable for the accuracy and integrity of the work. Naoki Kataoka contributed to the work, assisted in the revision of the content, approved the final version to be published, and agreed to be accountable for the accuracy and integrity of the work.

Funding Statement

The researchers did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data Availability Statement

All data generated or analyzed during this study are included in this published article and its online supplementary material files. Further inquiries can be directed to the corresponding author.