Non Hodgkin Lymphoma in Supraglottis: Case Report

Primary hematologic larynx malignancies are rare. Lymphoma represents less than 1% of malignant laryngeal tumors with the B-cell phenotype as the predominant. Fewer than 100 cases of primary laryngeal lymphoma have been reported in the global literature [1–3].

Initially, the patient may present dysphagia, dysphonia, dyspnea, and cervical lymphadenopathy. Systemic symptoms (fever, weight loss and sweating) and lymph nodes are not necessarily included. Indirect laryngoscopy usually reveals a polypoid submucosal supraglottic mass, nonulcerated, with no specific diagnostic features. The diagnosis rests on the histological examination of a biopsy specimen [1,4].

We report a case of primary laryngeal non-Hodgkin's large cell B lymphoma from supraglottis.

A 23 years old man consulting for globus sensation and hoarseness associated to vocal fatigue, dysphagia for solids and dyspnea exacerbated after great effort. The condition was started two months earlier. He had no history of fever, night sweats, or weight loss. There is no history of comorbidities and medication use, smoking and alcoholism.

In the neck palpation, there was a cervical lymph node in right level IIa about 3 cm size, it was moveable, soft and painless. The Waldeyer ring was clinically normal. The flexible nasofibrolaryngoscopy (Figure 1), a submucosal mass of the right aryepiglottic.

Figure 1: Nasofibrolaryngoscopy: Submucosal mass of the right aryepiglottic fold, which extended to the right piriform sinus, was noted, showing hyper vascular aspect with friable areas.

Laboratory tests did not show changes in peripheral blood and the serology for Cytomegalovirus, Epstein Barr virus, rubella, syphilis, HIV and toxoplasmosis were all negative.

Computed tomography imaging (Figure 2) had any specific characteristic that could distinguish from any larynx mass. Also, noted a cervical lymph node right level II measuring 3.9 × 3.0 × 2.2 cm. A PET-CT was performed showing only this supraglottic mass and neck lymph node at right as we can see in Figure 3.

Figure 2: Neck CT scan: homogeneous laryngeal mass at right aryepiglottic fold that extends to the extralaryngeal area on the rigth side and narrows to the right piriform sinus in the neck.

Figure 3: Coronal PET-CT image, before treatment, demonstrates avid FDG uptake in supraglottis at right about size of 1,6 cm and SUV 22,1 and a right neck lymph node mass levels II and III about size of 4,9 × 3,0 cm and SUV 28.

Under general anesthesia, the patient underwent direct microlaryngoscopy for endoscopic biopsy. Fragmented tissue biopsies measuring 0.5 × 0.5 cm in diameter were received. Histologically, the tumor resulted in non-Hodgkin`s large B cell lymphoma with high proliferative index (Figure 4). Immunohistochemistry it was positive for CD45, CD20, CD10, BCL6, Ki67 and negative for AE1AE3, CD3 and Bcl2 (Table 1).

Figure 4: Histopathological study, A) Stained with hematoxylin and eosin showing lymphoma cells, B) CD3 immunohistochemistry showing that only normal T lymphocytes (small) positive, while neoplastic (large) were negative, C) Immunohistochemistry showing positivity for CD20 (B cells), D) Immunohistochemistry showing positive for CD45 (leukocyte common antigen).

Table 1: Details of the immunostaining and hybridization: Immunohistochemistry.

The patient was referred to the hematology service for specific treatment. After a negative bone marrow biopsy (Figure 5), he was given three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and after sessions of chemotherapy with no complications he was considered free from disease. In control examination, there were no signals of the lesion and no complains. A PET-CT (Figure 6) was performed six months after treatment and there were no more lesions.

Figure 5: Histopathological study of bone marrow biopsy stained with hematoxylin and eosin, 200x magnification, normal exam.

Figure 6: PET-CT image, after treatment, demonstrates no FDG capitation.

Non-Hodgkin's lymphoma (NHL) is the second most common hematologic tumor in the larynx, after plasmacytoma [5]. The diagnosis is a challenge, since patients present with unspecific symptoms such as dysphonia, dysphagia and odynophagia and, initially, lymphadenopathy and other systemic symptoms such as fever, night sweats and weight loss are not present [1,4].

Male are more affected than female and the age at onset range from 4 to 81 years, with the mean age of occurrence to be the seventh decade [6,7]. Initial symptoms include hoarseness, dysphagia, globus sensation, stridor, or systemic signs, such as weight loss and fever. Laryngeal lymphomas tend to remain localized for a long period without progress of symptoms. Chemotherapy and radiation therapy are the most common therapeutic strategies advocated worldwide for laryngeal lymphoma treatment.

Supraglottis is the main larynx site of primary NHL Lymphomas because it contains follicular lymphoid tissue [1,8]. Diffuse large B-cell and mucosa associated lymphoid tissue (MALT)-type marginal zone B-cell lymphomas are the most commonly found primary laryngeal hematopoietic neoplasms [1,3]. Other types of lymphomas, such as Tor natural killer (NK)-cell lymphomas, have rarely been reported. [1,9-13].

Computed tomography (CT) imaging show that lymphoma usually are tumors with homogeneous enhancement after intravenous contrast injection [3]. A large nonnecrotic supraglottic lesion with a submucosal component that demonstrates homogeneous enhancement is more characteristic of lymphoma than of squamous cell carcinoma. Laryngeal lymphoma is commonly seen to extend into the hypopharynx, but it can also be isolated to the supraglottis. Cervical lymphadenopathy, a common finding in supraglottic squamous cell carcinoma, is seen in a smaller percentage of patients with laryngeal lymphoma [2].

In recent years, the advent of new technologies that allow the subtyping and the understanding of molecular mechanisms, such as PCR and gene sequencing has allowed the identification of molecular signaling pathways and drug targets. Thus, added to the usual treatment of NHL, consisting of radiotherapy and/or chemotherapy, new therapies such as monoclonal antibodies like rituximab [5].

The diagnosis of NHL laryngeal is a challenge to the otolaryngologist, since, usually, patients present with nonspecific complaints and no systemic signs suggestive of this condition. Computed tomography can demonstrate nonspecific homogenous enhancement and nasofibrolaryngoscopy has no specific features. Direct biopsy makes the diagnosis.

It is an important consideration in the differential diagnosis of laryngeal tumors, as lymphoma is treated with chemoradiation instead of surgery.