History of present illness
A 44-year-old Caucasian man went to his general practitioner because of persistent swelling in the left submandibular area ( Fig. 9.1 ). The symptom disturbed him a lot, both aesthetically and because it affected chewing and swallowing. He was prescribed an ultrasound and then a magnetic resonance imaging (MRI) of the neck, which showed the presence of large confluent lymph nodes suspected of malignancies such as lymphoproliferative disease or metastases. The parotid gland had no morphological and/or structural changes. An enlargement of the inferior nasal turbinate was also found.
A couple of weeks later, the patient underwent biopsies of a lateral cervical lymph node and the nasal mucosa. In both sites, chronic granulomatous inflammation with lymphocyte prevalence and some necrotizing areas were found. The acid-fast bacilli (AFB) smears were negative, and cultures showed no mycobacterial growth. Then, the patient underwent a chest-abdomen computed tomography (CT) scan with intravenous contrast medium ( Fig. 9.2 ). This showed bilateral pulmonary nodules with centrilobular distribution and “tree-in-bud” pattern, most evident in the middle lobe. Enlarged partially necrotic lymph nodes were found in the mediastinum. There was no pleural or pericardial effusion. In the right kidney, there was a small (5 mm) nonobstructing kidney stone.
Active tuberculous was suspected; thus, the patient was admitted to the pulmonology ward.
Past medical history
The patient was a lifelong nonsmoker, without previous significant exposure to noxious particles or gases. His body mass index (BMI) was normal (height 178 cm, weight 71 kg, BMI 22.4), and he had no recent weight loss or reduced appetite. No drug or inhalant allergies were known. He had no contact with people who had pulmonary tuberculosis or other respiratory infections.
He suffered from nephrolithiasis and underwent extracorporeal shock wave lithotripsy due to a calcific kidney stone in his right kidney. He also had a deviation of the nasal septum and turbinate hypertrophy. He was not on any medication at the time of evaluation.
Physical examination and early clinical findings
At admission, the patient had no fever (body temperature was 36.5°C [97.7°F]). In addition to the symptoms related to neck swelling, he complained of exertional dyspnea, sporadic dry cough, and a somewhat stuffy nose. Oxygen saturation (SpO 2 ) was 97% while at rest in room air, with a respiratory rate of 17 breaths/min. Blood pressure was 130/85 mmHg, and heart rate was 75 beats/min.
Chest examination revealed no pathological sounds. No clubbing or peripheral edema was observed.
Blood tests showed a mild increase in inflammation indices (C-reactive protein [CRP] 35 mg/L; normal values < 5 mg/L), normal white blood cell (WBC) count (6,450 cells/μL), and normal differential count. Basic autoimmunity blood pattern (antinuclear antibodies, extractable nuclear antigen, anti-neutrophil cytoplasmic antibody) was negative.
Arterial blood gas analysis confirmed normal respiratory exchanges at rest (pH 7.41, pO 2 89 mmHg, pCO 2 36 mmHg).
Clinical course
During hospitalization, tuberculin skin test and QuantiFERON-TB test were performed and turned out negative. The search for HIV antibodies was negative, too. Serum angiotensin-converting enzyme (ACE) levels were normal (40 μg/L, suggested cutoff 68 μg/L), whereas the soluble interleukin 2 receptor (sIL-2R) was slightly increased (3760 pg/mL, suggested cutoff 3550 pg/mL).
A bronchoscopy with BAL was performed. A total volume of 200 mL of saline was instilled in the middle lobe (4 × 50 aliquots), with a satisfactory fluid retrieval (110 mL).
No ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) attempt was made as the patient had a worsening cough during the procedure, despite sedation (intravenous midazolam 7 mg) and instillation of local anesthetic into the upper airways (lidocaine 2%).
Since inflammatory indices slightly raised (CRP 62 mg/L), empiric antibiotic therapy was started just after the bronchoscopy (ceftriaxone 2 g/day intravenously).
BAL fluid analyses revealed lymphocytic alveolitis (lymphocytes 85%), with an increase in the CD4 + :CD8 + ratio (7.8; normal value < 2). A nucleic acid amplification test (NAAT) for Mycobacterium tuberculosis complex was negative, as well as the acid-fast bacilli smear. No malignant cells were found on cytology. The general culture examination did not show the growth of microorganisms, and the search for the galactomannan antigen was negative.
In the following days, a total body PET/CT scan ( Fig. 9.3 ) showed a moderate FDG uptake of mediastinal lymph nodes, particularly in the left paratracheal, pretracheal, and subcarinal areas (maximum standardized uptake value [SUV max ] 4–6.2) and in bilateral pulmonary hila (SUV max 3.9 on the right). A minimal accentuation of radiopharmaceutical uptake (SUV max 1.8) was also present at the nodules with tree-in-bud appearance in the right upper lobe, the middle lobe, and the lateral basal segment of the left lobe.
An entire laterocervical lymph node was removed (excisional biopsy). Histology was negative for malignancy and confirmed the presence of a focal necrotizing granulomatous inflammation ( Fig. 9.4 ). A polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis was negative.
