IgG4 inflammatory pseudotumor mimicking primary lung cancer a case report

Abstract

Introduction:

IgG4 related disease (IgG4-RTD) is an infrequent disease with possible multiple organ involvement. It is characteristic to find inflammatory nodules with IgG4 positive plasma cell infiltration, storiform fibrosis and obliterative phlebitis. We present a patient with an inflammatory pseudotumor in the right upper lobe, mimicking a primary lung tumor.

Case report:

Our patient, a 48-year old heavy smoker (25 pack/year) with no relevant medical background, referred chest pain, non-productive cough and sporadic nightly fever. Image findings revealed a mass in the right upper lobe, with increased SUV in PET-scan, and mediastinal lymphadenopathies. Primary lung tumor was suspected and right upper lobectomy was performed. Due to absence of cellular atypia and the intense plasmacytic activity in the lesion, immunohistochemical analysis was performed: abundant IgG4 plasma cells were identified, with a IgG4/IgG relation of 74%. Diagnosis of IgG4- inflammatory pseudotumor was made.

Discussion:

After an extensive bibliographic review, we found just one similar case reported with an IgG4-lung pseudotumor without systemic disease. Due to the broad spectrum of clinical features of IgG4-RTD, and the potential multiple organ involvement, it is hard to find a classification and diagnostic criteria with high sensitivity and specificity, nevertheless they can be useful in clinical practice.

Conclusion:

There are several benign inflammatory diseases which can mimic a primary lung tumor. Although incidence is low, IgG4 pseudotumor should be considered as a differential diagnosis in the absence of malignancy.

La enfermedad relacionada a IgG4 es una entidad autoinmune infrecuente de compromiso multiorgánico con posible afectación pulmonar. Suele presentarse en el sexo masculino a edades avanzadas. Presentamos el caso de una paciente con una masa pulmonar en el lóbulo superior derecho, de características clínicas e imagenológicas similares a un tumor primario de pulmón. El diagnóstico definitivo se realizó con los hallazgos de la histopatología, en la cual se evidenciaron infiltrados linfoplasmocitarios con predominio de células plasmáticas IgG4 positivas.

Por esto consideramos que, en los casos de masa pulmonar sin evidencia de atipias celulares la enfermedad por IgG4 es un diagnóstico diferencial a tener en cuenta.

Conceptos clave

Qué se sabe sobre el tema:

La enfermedad relacionada con IgG4 fue descrita en los años '90 y se caracteriza por su compromiso multiorgánico y presentación clínica variable, por lo cual se establecieron múltiples criterios diagnósticos y clasificaciones. A nivel pulmonar se puede presentar como neumonía intersticial, adenopatías mediastinales y pulmonares o pseudotumor inflamatorio. El diagnóstico se confirma con el estudio histopatológico por la presencia de infiltrados de células plasmáticas y tiene buena respuesta al tratamiento con corticoides.

Qué aporta este trabajo:

El caso presentado a continuación es de un paciente con un pseudotumor inflamatorio en el vértice pulmonar derecho sin compromiso sistémico que simula un tumor primario de pulmón. Si bien constituye una presentación clínica atípica, consideramos que se debe tener en cuenta al pseudotumor por IgG4 como diagnóstico diferencial de masa pulmonar, una vez descartada la causa neoplásica.

Introduction

IgG4 related disease (IgG4-RTD) is an infrequent disease which most commonly affects elderly male patients, originally described in the 1990s. Several reports show evidence of multiple organ involvement, such as salivary glands, orbital structures, pancreas and kidneys, among others. It is characteristic to find inflammatory nodules with IgG4 positive plasma cell infiltration, storiform fibrosis and obliterative phlebitis ¹ . In the year 2019 a new classification was proposed by the American College of Rheumatology and the European League Against Rheumatism ² .

Pulmonary IgG4 related disease has a wide spectrum, and may present itself as nonspecific interstitial pneumonia, inflammatory pseudotumor or lymphadenopathies ¹ . We present a patient with an inflammatory pseudotumor in the right upper lobe, with no evidence of extrapulmonary involvement, clinically indistinguishable from a primary lung tumor.

Case Report

We present a 48-year old heavy smoker (25 pack/year) with no relevant medical background. His chief complaint was a low intensity, constant chest pain, with non-productive cough and sporadic nightly fever.

Chest x-ray revealed a radiopaque mass in the right upper lobe without pleural effusion, pneumotorax or lung consolidation (figure 1). SARS-Cov2 infection was ruled out by polymerase-chain-reaction. CT-scan showed an irregular mass with spiculated edges of 47 x 50.5 mm and pleural retraction, along with pathological mediastinal lymph nodes (over 10 mm) (figure 2).

Figure N °1. Initial chest x-ray. X-ray showing an area of increased density in the upper right lobe, near the vertex, with no evidence of associated pleural effusion or pneumothorax.

Figure N °2. Preoperative non-enhanced computed tomography showing mass of 47 x 50.5 mm in axial (C, D) and coronal (A, B) planes, which is in intimate contact with the esophagus.

Tumor staging studies were performed: PET-scan showed increased uptake of the lung mass (SUV 10) and mediastinal and hilar lymph nodes with a slightly increased uptake (2.8 and 3.9 SUV respectively) (figure 3). There was no evidence of disseminated disease in the PET-Scan or brain-MRI.

Figure N °3. Pet-scan showing increased SUV in already known mass in right upper lung vertex (SUV 10) (A, C) and mediastinal and right hilar subcentimeter lymph nodes (SUV 2.8 and 3.9) (B). No other organs with pathological findings were evidenced by this method.

Given the patient's history and imagenological findings, locally advanced primary lung tumor was suspected. Esophageal ultrasound (EUS) was performed, with no evidence of esophageal infiltration.

Prior to oncological resection, lymph node biopsy of groups 2R, 4R, 4L and 7 (which had high uptake on PEt-scan) was performed by videomediastinoscopy. Pathology results were positive for antracosis, with no signs of cellular atypia. The case was discussed in a multidisciplinary committee and surgical resection was decided.

Video assisted thoracoscopic right upper lobectomy with lymphadenectomy was performed. The patient had no immediate complications, and spent 72 hours in the intensive care unit for routine monitoring. The patient was discharged on day six. 15 days later, postoperative control showed no late complications.

Histopathologic study revealed an inflammatory process with necrotic areas and lymphoplasmacytic infiltration. The entire lung mass was thoroughly analyzed in his whole extension (4,5 x 3,2 cm) and no cellular atypia were found. Anthracosis and reactive changes were found at the lymph nodes.

Due to the absence of atypical cells and the intense plasmacytic activity in the lesion, immunohistochemical analysis was performed: 294 IgG positive plasma cells per high-power-field (HPF) and 219 IgG4 plasma cells per high-power-field were identified, with a IgG4/IgG relation of 74%. Figure 4.

Figure N °4. Tissue samples of the lung mass. A: dense lymphoplasmacytic infiltration with eosinophils (Hematoxylin and eosin staining, original magnification x400). B: IgG positive plasma cells evidenced with immunostaining in a high power field (immunohistochemistry, original magnificaction x400). C: IgG4 positive plasma cells evidenced in a high power field (immunohistochemistry, original magnification x400).

With these findings, diagnosis of IgG4- inflammatory pseudotumor was made. Serum IgG4 levels were measured, with a total of 244 mg/dL, superior to reference range.

Discussion

IgG4 related disease with lung involvement is uncommon and is usually seen in cases of multiorganic affection ³ . After an extensive bibliographic review, we found but one similar case reported, of a japanese woman with an IgG4-lung pseudotumor without systemic disease ⁴ .

In the year 2011 the comprehensive Criteria for IgG4 related disease were proposed ⁵ . These include: a) swelling or masses in single o multiple organs, b) elevated levels of serum IgG4 (>135mg/dL), c) lymphocytic and plasmacytic infiltration and fibrosis in histopathologic analysis or presence of IgG4 plasma cells. When criteria A. and C. are met, the diagnosis of IgG4 related disease is probable. If the IgG4 serum levels are elevated, the diagnosis is definite. Our patient fulfilled all of the criteria: a lung mass with marked lymphoplasmacytic infiltration and fibrosis, associated with high IgG/IgG4 proportion (74%) and IgG4-serum levels of 244 mg/dL.

The American College of Rheumatology and the European League Against Rheumatism developed a new classification for IgG4-RTD in the year 2019. These criteria were proposed by a multispecialty group of 86 physicians based on a cohort of 1879 patients and the existing literature. Our patient patient would not be classified as having IgG4-RTD following this classification because of meeting some of the exclusion criteria (fever and radiological findings suspicious of malignancy) and not presenting the inclusion criteria of lung involvement (e.g. peribronchovascular or septal thickening evidenced in cross-sectional image study or paravertebral band-like soft tissue). However the diagnosis was confirmed by histopathological and immunohistochemical analysis.

Due to the broad spectrum of clinical features of IgG4-RTD, and the potential multiple organ involvement, it is hard to find a classification and diagnostic criteria with high sensitivity and specificity. Even though the classifications published in the literature can be useful in clinical practice, one must take into account that some cases do not necessarily fulfill the criteria to be considered as IgG4-RTD, like our patient.

There are several benign inflammatory diseases (e.g. sarcoidosis, Castlemann disease) which can mimic a primary lung tumor. Although incidence is low, IgG4-RTD presenting as a lung pseudotumor without other organ involvement is a differential diagnosis to be considered in the case no malignancy is found. When IgG4-RTD is diagnosed, corticosteroids are the first line treatment, showing improvement of radiological findings and symptoms.

Conclusion

IgG4 related disease is an infrequent and variable disease which can mimic a primary lung tumor. Even though incidence is low it is a differential diagnosis to be considered, once malignancy is ruled out. Several classifications and diagnostic criteria published in the last years are useful to identify this disease. However, not all of them suited our patient and IgG4-RTD was confirmed upon/with pathological findings.