This is a case report about the non-caseating necrotizing granulomatous  inflammation of the lingual tonsil. Without any past medical history, a young woman  presented with severe dysphagia and difficult of breathing. No malignancy or abscess  was found. However, the inflammation was resistant to treatment and it required  repeated high doses of corticosteroids. After a detailed throughout diagnostic scan,  mononucleosis was claimed to be the most possible causative agent of the noncaseating necrotizing granulomatous inflammation.

• Glossal tonsil

• Inflammation

• Orofacial Granulomatosis

• Granulomas

• Sarcoidosis

Bizaki A, Salonen T, Numminen J, Rautiainen M (2016) Granulomatous Hypertrophy of the Lingual Tonsil. Ann Otolaryngol Rhinol 3(8): 1123.

EPG: Epithelioid Granulomas; RSV: Respiratory Syncytial Virus; EBV: Epstein-Barr; CMV: Cytomegalovirus; HIV: Human Immunodeficiency Virus, WBC: White Blood Cells; CRP: C-Reactive Protein; ACE: Angiotensin Converting Enzyme; MRI: Magnetic Resonance Tomography; CT: Computer Tomography; CCPAb: Cyclic Citrullinated Peptide Antibody; ENT: Ear Nose and Throat; PPI: Proton Pump Inhibitor; RF: Rheumatoid Factor.

Granulomas are noticeably complex inflammatory foci that sequester organisms or other substances that are resistant to degradation. While a large number of granulomatous disorders are recognized, infections are clearly the most common underlying causative agents of granulomas [1]. Waldeyer’s tonsillar ring is uncommonly affected by granulomatous inflammation. Orofacial granulomatosis characterized by noncaseating granulomatous inflammation affecting the soft tissues of the oral and maxillofacial region. It has been strongly associated with Crohn’S disease [2-11]. Based on a Japanese study, three types of epithelioid granulomas (EPG) have been identified: (i) poorly demarcated small epithelioid cell granulomas; (ii) welldemarcated non-caseating sarcoid-like granulomas; and (iii) EPGs with suppurations at the center [12].

Based on other study gram-positive cocci that included a streptococci are not usually causative agents of tonsillar granulomatous inflammation [13]. The causative form of tonsillar EPGs having central suppurations remains unclear. It seems that tonsillar EPGs are not so common and they show histological variation. According to histochemical and clinical follow-up information, the etiology of granulomas includes Sarcoidosis, Tuberculosis, Hodgkin’s lymphoma, Toxoplasmosis and Squamous cell carcinoma. However, in a large number of cases, the cause remains unknown [14].

Patient history

A healthy 24-year-old woman presented with dysphagia, sore throat, high fever and abdominal pain that had lasted for a week, in addition to some subjective shortness of breath. The patient had no allergies and, with the exception of oral contraceptives, took no medication. Tonsillectomy was performed at the age of 16 (because of hypertrophy) and appendectomy at the age of 18 (the appendix was normal but mesenteric lymphadenitis was found).

Clinical examination

Clinical examination at the time of initial presentation, revealed neck lymphadenopathy, a swollen lingual tonsil covered in white spots, purulent mucous in the nasopharynx and edematous epiglottis. There was also some redness in the mucosal of the oropharynx. Indirect laryngoscopy and flexible laryngoscopy revealed normal cords and arytenoid cartilages.

Laboratory tests

Blood test results revealed severe leukocytosis (WBC = 29.6 x 10E9/l), elevated c-reactive protein (CRP = 37 mg/l) and liver enzymes (ALAT = 481U/l, ASAT = 288 U/l, AFOS = 472U/l, GT = 283U/l, Bilirubin = 45U/l). Mononucleosis antibodies were positive.

Diagnosis

Based on clinical examination and laboratory tests, the patient was initially diagnosed with mononucleosis.

Treatment

Throat culture was taken and the patient was admitted to an inpatient ward and empiric antibiotic treatment with G-penicillin (2millions units IU x 4 intravenously) was started. Additionally, Oradexon (10 mg x 2 intravenously) and ketoprofen 100 mg 2 times per day intravenously were also administered. The following day prednisone was started (20 mg per day per os). An abdominal ultrasound scan was taken and esomeprazole (40 mg x 1 per os) was started. Four days after admission, the patient was discharged with a prescription for penicillin (1500 mg per os two times per day) and ketoprofen 100 mg 3 times per day.

Patient’s clinical course was unusual since after initial presentation and patient several times repeatedly developed the same symptoms. Patient was admitted within 6 months in total 4 times in the ward because of dysphagia, sore throat and subjective shortness of breath. There was no stridor at any point. Fever was present at the time of first and third admission. Since swelling of epiglottis and lingual tonsil were present, patient received high doses of corticosteroids intravenously and per os. There was no swelling of the vocal cords at any point and airway was patent. Each admission lasts between 4 to 7 days. CRP was elevated every time that patient was admitted. Leukocytosis was present during the first, third and fourth admission of the patient. Since patient had fever and inflammation parameters were elevated, patient received in total two courses of intravenous antibiotics and five courses of antibiotics per os. Along with a follow-up appointment between the second and third admission, a neck MRI was taken and it revealed a hypertrophy of lingual tonsil and neck lymphadenopathy. During the third admission of the patient in the hospital, patient complained also for tenderness to her ankles. A thorax x-ray showed no pulmonary infiltrates but visualization of the bronchus close to the hilum of the lung was prominent. During the admission, patient’s dysphagia and airway symptoms were more prominent. Thus, different laboratory tests were carried out to exclude diseases such as sarcoidosis and vasculitis. A computed tomography (CT) body scan was ordered. CT imaging showed one solitary condensed triangularshaped 6-mm shadow in right lung (in the middle lobe). In the left ovary, there was a 2.8 cm x 4 cm cyst. In SI-joints, there was some mild sclerosis. No pathological lymphadenopathy was found. Three days later, a biopsy was taken from the lingual tonsil. Histopathological examination of lingual tonsil, revealed the presence of necrotizing granulomatous inflammation (non caseating granulomas with giant cells). There was no evidence of sarcoidosis and tuberculosis was excluded figure 1.

Figure 1: Magnetic resonance imaging revealed hyperthophy of the lingual tonsil neck lymphadenopathy.

An ultrasound of ankles was performed during the fourth admission and it revealed a tendonitis of Achilles tendon bilaterally. According to internal medicine physicians, tenosynovitis was found in the ankles and confirmed with an ultrasound scan. The tibialis posterior area was positive for tenosynovitis in Doppler ultrasound examination. The Achilles-tendons were treated locally with an injection of methyl prednisone (Depo-Medrol) and lidocain. A MRI scan of the sacroiliac-joints was ordered, and the findings for sacroiliitis were negative figure 2.

Figure 2: Examination with a flexible nasofiberoscope, the image shows swelling of the lingual tonsil and also swelling in the arytenoids.

Further laboratory tests that included respiratory syncytial virus (RSV), Epstein-barr (EBV), cytomegalovirus (CMV), human immunodeficiency virus (HIV) and throat culture were carried out. The blood tests were positive for streptococcus, adenovirus and CMV. During the third admission, detailed laboratory test results revealed mild leukocytosis with 38% lymphocytes, Mild Thrombocytosis, Microcytic anemia, high levels of ferritin (Table 1).

Table 1: Symptoms, Findings and Diagnostic Work-Up.

Even though CMV and EBV IgG and IgM were positive, tests for CMV and EBV DNA were negative. The angiotensin-converting enzyme (ACE) and complement tests were also slightly elevated (Table 1). Lysozyme was normal in high border (=1.6u/l). Lysozyme and ACE may be increased in cases of sarcoidosis however sarcoidosis was excluded based on histopathological examination of lingual tonsil. Oxiklorin was started for the treatment of tenosynovitis during the fourth admission into the hospital based on rheumatologist’s guidance. Calcium tablets,Further laboratory tests that included respiratory syncytial virus (RSV), Epstein-barr (EBV), cytomegalovirus (CMV), human immunodeficiency virus (HIV) and throat culture were carried out. The blood tests were positive for streptococcus, adenovirus and CMV. During the third admission, detailed laboratory test results revealed mild leukocytosis with 38% lymphocytes, Mild Thrombocytosis, Microcytic anemia, high levels of ferritin (Table 1). Even though CMV and EBV IgG and IgM were positive, tests for CMV and EBV DNA were negative. The angiotensin-converting enzyme (ACE) and complement tests were also slightly elevated (Table 1). Lysozyme was normal in high border (=1.6u/l). Lysozyme and ACE may be increased in cases of sarcoidosis however sarcoidosis was excluded based on histopathological examination of lingual tonsil. Oxiklorin was started for the treatment of tenosynovitis during the fourth admission into the hospital based on rheumatologist’s guidance. Calcium tablets,vitamin D and PPI-medication were given during prednisone treatment. Prednisone was prescribed per os with a taper-off dose until follow-up examination, which was scheduled for about one month later figure 3.

Figure 3: Pathological examination of the lingual tonsil showed noncaseating necrotizing granulomatous inflammations.

Based on the examinations, an autoimmune disease was suspected and treatment continued in the department of rheumatological diseases. Three months later, a follow-up thorax CT scan revealed no changes in the previous findings. At the same time, the patient’s ENT status was checked and the patient was free of symptoms. Based on the guidance of a doctor of internal medicine doctor, a colonoscopy was performed at the same time in order to exclude autoimmune diseases such as Crohn’S disease. Oxiklorin was gradually discontinued a month later. Four months after the discontinuation of oxiklorin, the patient contacted our clinic because of a 2-day sore throat. Before that and for about 6 months, she had not had any otolaryngological symptoms. In clinical examination, the lingual tonsil was slightly swollen, but otherwise the larynx and otolaryngological status were normal. In blood tests, inflammatory parameters were normal.

The patient’s case was discussed in a multi-specialty meeting, but no further intervention or treatment was scheduled. Three months later, the patient came again to the emergency room with a feeling of swelling in the throat. In otolaryngological clinical examination, the base of tongue was swollen and the lingual tonsil was hypertrophic. There was no neck lymphadenopathy and no findings in the larynx. Prednisone was once again prescribed to the patient for a few days in a low dose. However, patient did not need further examination or admission since she remains otherwise free of symptoms.

Waldeyer’s ring is uncommonly affected by granulomatous inflammation. Infection seems to be a common causative agent. However, in many cases, it may be part of a systemic disease such as sarcoidosis, Crohn’s disease [2-11], fungal infection or tuberculosis [15-17]. In the case of tonsillar granulomas that are not associated with chronic tonsillitis or recurrent tonsillar infection, the presence of systemic disease should be excluded. Sarcoidosis is characterized by the presence of noncaseating granulomas and orofacial manifestations of the condition have been reported [18,19]. However, a pathologist confirmed that our case was not sarcoidosis. Tuberculosis and malignancy were also excluded.

The interest point of this case is that granulomatous inflammation without malignancy is extremely rare in oropharynx. Even tonsillectomy had been previously performed; lingual tonsil and supraglottical structures were inflamed and swollen, causing severe symptoms as dysphagia and shortness of breath. Patient needed repeated high doses of corticosteroids and also immunosuppressive medications as oxiklorin in order to control the inflammation. Since systemic diseases had been excluded, mononucleosis was the most likely causative agent of granulomatous inflammation of the lingual tonsil.

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