* ENT Department, “Gr. T. Popa” University of Medicine and Pharmacy Iasi, Romania* ENT Department* Histopathology Department* Radiodiagnostic Department* Oncology Department/Anatomy Department/Pneumology Hospital, Iasi
Introduction
Malignant Non Hodgkin’s Lymphoma of the larynx represents a rare disease (there were only 90 cases mentioned in the anglo-saxon literature until 2006). (1) The first case of laryngeal non Hodkgin lymphoma was mentioned in 1934 by Mac Kenty and Remacle, the disease being more frequent amongst adult and having the histopathologic aspect of a type B lymphocitary cell. (2)
The symptomatology in the laryngeal localization is represented by dyspneea, dysphonia or dysphagia, only rarely causing acute respiratory failure phenomena. In time, it can determine extralaryngeal extension in the respiratory tract, skin and stomach. (3,4,5) The diagnosis includes ENT exam (indirect and direct laryngoscopy, fibroscopy), radiological exams (CT, MRI) and histopatological confirmation.
The updated Keil classification is used nowadays for dividing the non Hodgkin’s Lymphoma in 4 stages as follows: Stage I E – strictly laryngeal localization of non Hodgkin’s lymphoma; Stage II E – laryngeal and regional lymphatic nodes involvement; Stage III E – generalized head and neck disease; Stage IV E – secondary laryngeal affection inside of a generalized disease.
The treatment options depend on a variety of factors including the grade of lymphoma, the stage and extent of disease, the patient status. (6,7,8)
Case report
The authors present a case of I.F., a 25 year old male pacient admitted in our ENT Department with a severe acute respiratory insufficiency by transfer from the Pneumology Hospital Iasi. Emergency tracheotomy was required. Previously, the patient had been suspected with asthma due to the presence of progresive dyspneea, dysphonia and productive caughing. The tracheobronchofibroscopy identified a vegetant tumoral mass, arising from subglottic larynx and trachea. During an accidental fall of the patient, the tumor migrated between the vocal cords causing airway obstruction which required tracheotomy. (fig. 1) The CT scan confirmed the presence of the tumor originating from the subglottic larynx and anterior wall of upper cervical trachea (first tracheal ring) protruding into the larynx tracheal lumen. Systemic screening found no other extra-laryngeal tumoral lesions. (fig. 2)
Results
The surgical management was decided according to the tumoral mass, under general anesthesia, by external approach. The median thyrotomy was performed with the outlining of the mobile pediculated tumor located in the subglottic region on the anterior side of the cricoid cartilage and the first tracheal ring. (fig. 3,4,5,6)
We decided to excise the tumor by external approach as we considered that we will have a better view, like the one we have in the endoscopical approach. The tracheotomy was suppressed after 48 hours due to favorable postoperatory prognosis with normal breathing and disappearance of dysphonia. The histopathological exam of the surgical specimen showed a large anaplastic B cell lymphoma with a proliferation of large atyipical cells with vesicular chromatin, proeminent nucleoli and bizare shaped nuclei in the lamina propria . These aspects can lead to other types of malign lymphoma and carcinoma, requiring the immunohistochemical exams (fig. 7,8,9).
The phenotype was identified in the paraffin sections and included CD 30+ (fig. 8) CD 30 ± (fig. 9) focal and CD 20 (fig. 10).
The differential diagnosis is important to exclude the other types of non lymphoid malignancies.
The absence of other extralaryngeal lesions and lymphadenopathy included the patient in the stage IE.
In present, the most used prognosis classification of diffuse lymphoma with large cells is the International Prognostic Index (I.P.I.) that can predict the evolution of patients with aggresive non Hodgkin’s lymphoma.
Five factors are of the same value and have independent influence on the patient’s survival: age > 60 years, values LDH > 2, Ann Arbor stage III or IV, the presence of > 2 extranodal sides. According to I.P.I., this patient with 0 risk factors was included in the good risk category with » 80% chances of survival 10 years after the treatment. (10,11,12)
After surgery, the treatment was completed with combined chemotherapy and radiotherapy.
The chemotherapy consists on 4 cycles of CHOP (Cyclophosphamide, Adriamycine, Vincristine, Prednisone) every 21 days, followed by local external radiotherapy in dose of 30 Gy. The first 4 cycles of chemotherapy were well tolerated by the patient without any notable hematologic toxicity (grade 1). At the review exams, the patient maintains a very good general status without any biological modification.
After radiotherapy, the patient has been reviewed and underwent 2 more CHOP chemotherapy cycles.
Discussion
In the presented case of subglottic laryngeal non Hodgkin’s lymphoma (NHL), the initial symptomatology was confounded with pseudoasthmatiform phenomena because of progressive dispnea, productive coughing.
In evolution, the laryngeal obstruction caused by lymphoma may be mistaken for other tumoral lesions.
The histopathological exam of the surgical pieces can confirm the diagnosis of type B malignant lymphoma, with large anaplastic cells, having a high malignancy, classified as follows NHL classification.
Lymphoma with B lymphocitic cells: low malignancy: lymphocitic, lymphoplasmocitic, plasmocitic, centroblastic type; high malignancy: centroblastic, immunoblastic, lymphoblastic and with anaplastic cells type.
Lymphoma with T lymphocitic cells: low malignancy: lymphocitic and pleomorphic with small cells type; high malignancy: lymphocitic, immunoblastic, pleomorphic with large cells type.
The Ann Arbor classification was used to specify the treatment of laryngeal NHL:
a) NHL strictly localized requires locoregional radiotherapy 35-40 Gy. (13,14,15);
b) NHL in stage IE and IIE with a large tumoral mass requires chemotherapy associated with radiotherapy;
c) NHL in stage IIIE, IVE requires polichemotherapy;
d) NHL in localized form requires surgical excission.
The prognosis of the localized NHL form is favorable. The lymphatic spread with cervical lymphadenopathy and different secondary lesions determine a poor prognosis. (16,17,18)
Conclusions
Invasion of the subglottic larynx and trachea by lymphoma is an uncommon localization which can cause severe airway obstruction and requires a multidisciplinary approach.
Laryngeal NHL represents less than 1% of the primitive malignant laryngeal tumors, most of these having lymphocite B cells development.
Laryngeal NHL can remain located for a long time and the extent can occur later in the lymph nodes, respiratory tract, orbit, skin.
The CT scan, the histology as well as the immuno-histochemical exam confirm the tumoral form and extent in order to perform the complex therapy.
The characteristic feature of the presented case was the acute obstructive laryngeal syndrom caused by the protrusion of the mobile subglottic tumour into the glottic space requiring an emergency tracheotomy.
This case of laryngotracheal non Hodgkin’s lymphoma with low grade of cellular differentiation (anaplastic cells) required both surgical excision of strictly located tumor, combined by chemotherapy and radiotherapy.
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