What are the possible causes of chronic neck pain with reactive lymphadenopathy (enlarged lymph nodes) and diffuse soft tissue swelling in an adult patient, as seen on a computed tomography (CT) scan of the neck?

Differential Diagnosis of Chronic Neck Pain with Reactive Lymphadenopathy and Diffuse Soft Tissue Swelling

The combination of chronic neck pain, reactive lymphadenopathy, and diffuse soft tissue swelling on CT scan requires systematic evaluation for infectious, inflammatory, and neoplastic etiologies, with infection and malignancy being the most critical diagnoses to exclude urgently. 1, 2

Primary Diagnostic Categories

Infectious Etiologies (Most Common for Reactive Lymphadenopathy)

• Cervical lymphadenitis represents the most frequent cause of localized lymph node enlargement with surrounding soft tissue inflammation, typically from bacterial or viral pathogens affecting the upper respiratory tract or oral cavity 3
• Tuberculous lymphadenitis should be considered, particularly in patients with risk factors including immunosuppression, endemic exposure, or constitutional symptoms such as fever, night sweats, and weight loss 3
• Deep neck space infections (retropharyngeal, parapharyngeal, or submandibular space) can present with diffuse soft tissue swelling and reactive adenopathy, requiring urgent identification due to potential airway compromise 4
• Cat-scratch disease and other granulomatous infections may cause persistent lymphadenopathy with surrounding inflammation 3

Neoplastic Processes (Critical to Exclude)

• Metastatic disease to cervical lymph nodes from primary tumors (head and neck squamous cell carcinoma, thyroid cancer, lung cancer) frequently presents as neck mass with surrounding soft tissue changes 3
• Lymphoma (Hodgkin's or non-Hodgkin's) characteristically causes lymphadenopathy that may be accompanied by soft tissue infiltration and can present with constitutional "B" symptoms 5, 3
• Primary head and neck malignancies including thyroid carcinoma and salivary gland tumors can cause both mass effect and reactive lymphadenopathy 3

Inflammatory and Autoimmune Conditions

• Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome) can cause generalized or localized lymphadenopathy with soft tissue inflammation 6
• Sarcoidosis may present with cervical lymphadenopathy and soft tissue involvement 5
• Drug-induced lymphadenopathy should be considered in patients on certain medications (anticonvulsants, antibiotics) 6

Critical "Red Flags" Requiring Urgent Investigation

• Constitutional symptoms including fever, unexplained weight loss, and night sweats suggest infection, lymphoma, or metastatic disease 1, 2
• Elevated inflammatory markers (ESR, CRP, WBC) indicate active inflammatory or infectious process requiring immediate workup 2
• History of malignancy or risk factors for cancer (smoking, alcohol use, prior radiation) significantly elevate concern for metastatic disease 1, 2
• Immunocompromised state (HIV, transplant recipients, chronic steroid use) increases risk for atypical infections and malignancy 2, 3
• Progressive symptoms despite conservative therapy or rapidly enlarging lymph nodes warrant urgent tissue diagnosis 7, 6

Diagnostic Algorithm

Initial Clinical Assessment

• Document specific characteristics of the lymphadenopathy including size (nodes >1 cm warrant further evaluation), consistency (hard nodes suggest malignancy, fluctuant suggests abscess), mobility (fixed nodes suggest malignancy), and distribution (localized versus generalized) 7, 4
• Identify potential infectious sources by examining the oral cavity, pharynx, scalp, and skin for primary infection sites that could explain reactive adenopathy 3, 4
• Assess for systemic disease by evaluating for hepatosplenomegaly, generalized lymphadenopathy, and signs of autoimmune disease 7, 6

Laboratory Evaluation

• Obtain complete blood count with differential to assess for leukocytosis (infection), atypical lymphocytes (viral infection), or cytopenias (bone marrow involvement) 7
• Measure inflammatory markers (ESR, CRP) to quantify degree of inflammation 2
• Consider infectious serologies based on clinical suspicion (EBV, CMV, HIV, tuberculin skin test or interferon-gamma release assay) 3

Imaging Interpretation on CT Neck with Contrast

• Evaluate lymph node characteristics including size, number, presence of necrosis (suggests tuberculosis, malignancy, or suppurative infection), and enhancement pattern 4
• Assess soft tissue changes for phlegmonous enhancement (suggests cellulitis or early abscess), discrete fluid collections (abscess requiring drainage), or infiltrative patterns (suggests malignancy) 4
• Examine adjacent structures including the thyroid gland, salivary glands, aerodigestive tract, and vascular structures for primary pathology 4
• Scrutinize for deep neck space involvement which has serious implications for airway patency and potential intracranial or mediastinal extension 4

Tissue Diagnosis (Essential for Persistent Lymphadenopathy)

• Lymphadenopathy persisting >4 weeks requires tissue diagnosis to definitively exclude malignancy, with excisional biopsy preferred over fine-needle aspiration for suspected lymphoma to preserve architecture 7, 6
• Fine-needle aspiration cytology can be performed initially for suspected metastatic carcinoma or infectious processes 3
• Excisional lymph node biopsy is mandatory when lymphoma is suspected, as architectural assessment is crucial for accurate classification 7, 6

Common Pitfalls to Avoid

• Mistaking reactive lymphadenopathy for lymphoma is among the most frequent cancer misdiagnoses, emphasizing the critical importance of histological examination when clinical suspicion exists 6
• Assuming benign etiology without tissue diagnosis in adults with persistent lymphadenopathy (>4 weeks) risks missing malignancy, as the majority of generalized lymphadenopathy in adults represents hematological systemic disease 7
• Delaying imaging or tissue diagnosis in patients with red flag symptoms can result in progression of treatable infections or malignancies 1, 2
• Failing to correlate imaging findings with clinical presentation may lead to misinterpretation, as reactive changes are common and must be distinguished from primary pathology 4
• Inadequate tissue sampling (core needle biopsy instead of excisional biopsy for lymphoma) can result in non-diagnostic specimens requiring repeat procedures 7, 6