IgG4-related disease as an unexpected cause of hemoptysis

History of present illness

A 30-year-old never-smoker man was evaluated at the emergency department due to new onset of intermittent hemoptysis within a period of 4 weeks. Episodes increased in frequency, and the volume of expectorated fresh blood reached approximately 100 mL per day. The patient reported that a nonproductive cough had started 10 months before without any other systemic or thoracic symptoms. A chest radiograph in two planes revealed a hilo-mediastinal opacity with contact to the left upper lung lobe. A computed tomography (CT) scan of the chest with contrast material ( Fig 18.1 ) showed a peribronchovascular mass compressing the left main bronchus and the left pulmonary artery. There was no evidence of pulmonary embolism, lymphadenopathy, bronchiectasis, pneumonia, or pleural effusions. For further evaluation, the patient was referred to the Center for Interstitial and Rare Lung Disease, a tertiary pulmonary care center that is located at the Ruhrlandklinik University Hospital Essen, Germany.

Past medical history

The patient’s medical history was unremarkable except for gastroesophageal reflux disease, which was well controlled under omeprazole therapy. He reported no other medications. He had no known drug allergies and did not consume alcohol or illicit drugs. He lived with his wife in an urban area of western Germany and worked as an office assistant. There were no known occupational or inhalational exposures. No familiarity for malignancies, autoimmune disorders, or pulmonary diseases was reported.

Physical examination and early clinical findings

At referral to the hospital, body temperature was 36.8°C (98.24°F), heart rate was 75 beats/min, blood pressure was 124/82 mmHg, respiratory rate was 16 breaths per minute, and oxygen saturation was 97% while the patient was breathing ambient air at rest. Auscultation of the chest revealed no abnormalities. No peripheral cyanosis or edema was present, and there were no ecchymoses or other signs of bleeding.

The laboratory tests showed normal counts of white blood cells, eosinophils, and platelets. Total serum protein concentration and electrophoresis were in the normal range.

Blood levels of immunoglobulin E (IgE), electrolytes, lipase, amylase, lactate dehydrogenase, and C-reactive protein were normal, as were the results of liver function, kidney function, and clotting tests.

Lung function tests were all in the normal range, and the diffusing capacity of the lungs for carbon monoxide (DLCO) was 90% of the predicted value when corrected for hemoglobin.

A cranial CT scan showed no cerebral metastases, paranasal sinus abnormalities, or other abnormal findings.

A total body positron emission tomography (PET)/CT scan ( Fig 18.2 ) showed an increased ¹⁸ F-fluorodeoxyglucose ( ¹⁸ F-FDG) uptake of the peribronchovascular tumor (standardized uptake value [SUV] max. 12.3) but revealed no evidence of other ¹⁸ F-FDG–avid lesions.

Lung perfusion scintigraphy after the injection of technetium-99m ( ^99m Tc)-labeled macroaggregates of albumin revealed a pronounced left perfusion deficit with a mean activity distribution in the right lung of 92% compared to 8% in the left lung due to compression of the proximal left pulmonary artery by the tumor ( Fig 18.3 ).

Clinical course

ANA and ANCA tests were negative and there were normal serum levels of ACE (< 12 U/L, normal range 8–62 U/L) and sIL-2R (300 U/L, normal range 223–710 U/L).

A rigid diagnostic bronchoscopy with BAL, transbronchial core needle biopsies from the mass, and EBUS-TBNAs from suspicious lymph node stations was performed. Rigid bronchoscopy was chosen to facilitate the removal of preexisting blood clots and to optimize the management of potential bleeding complications in comparison to the use of a flexible bronchoscope. The left main bronchus was compressed by the surrounding tumor formation. Macroscopically, edema and hypervascularization of the mucosa, also involving the proximal left upper lobe bronchus, were seen. Forceps biopsy specimens were obtained from the visually altered mucosa of the left main bronchus and the left upper lobe bronchus. The mucosa was extremely vulnerable to manipulation with the bronchoscope and reacted with easy bleeding. There were no signs of active bleeding or endobronchial tumor growth. The remaining examination of the bronchial system was normal.

The recovered BAL fluid (BALF), obtained from the lingula, was clear, and the BALF differential cytology was normal. Perls Prussian blue staining revealed an increased number of hemosiderin-laden macrophages.

BALF staining for acid-fast bacilli was negative, and sputum polymerase chain reaction tests for tuberculous and nontuberculous mycobacteria were negative. An interferon-γ release assay revealed no prior immunization against mycobacterium tuberculosis.

Histological analysis of the tissue specimens obtained from the peribronchovascular mass showed a dense lymphoplasmacytic infiltrate, tissue fibrosis, and obliterative phlebitis accompanied by a mild granulocytic infiltrate. Lymph node TBNAs revealed unspecific inflammatory changes. Mucosal biopsy specimens of the left main and upper lobe bronchus showed signs of chronic bronchitis.

Because neoplastic cells in masses with extended inflammation or marked fibrosis can be missed by transbronchial core needle biopsy due to sampling bias, a surgical biopsy approach was recommended by the institutional tumor board to rule out malignancy with a higher negative predictive value.

Minimal thoracotomy was performed after placement of a double-lumen endotracheal tube for selective ventilation of the right lung. During palpation of the collapsed left lung, a centrally located solid mass was detectable and biopsy specimens were directly obtained from the tumor. The histological findings were compatible with the prior findings; again, there was no evidence of malignancy ( Fig 18.4 ).