Imaging Characteristics of Primary Laryngeal Lymphoma

Discussion

NHL most frequently arises in the gastrointestinal tract, but the head and neck is the second most frequent region.¹³ Most head and neck lymphoma arises within the Waldeyer ring, but extranodal extralymphatic sites still accounted for 25% of these tumors. The most common extranodal extralymphatic sites were the paranasal sinuses, the salivary glands, and the thyroid gland.¹⁴ The larynx is, thus, a rare site for a primary NHL.

NHL is presumed to arise from 2 locations within the larynx: 1) aggregates of specialized lymphoid tissue in the submucosa, predominantly of B-cell lineage, or 2) MALT, predominantly arising from the aryepiglottic folds and epiglottis.¹⁵ Fewer than 100 cases of lymphoproliferative tumors arising from the larynx (including both NHL and immunosuppression-related lymphoproliferative diseases) have been previously reported in the literature.⁴

The symptoms of NHL are typically site-specific and thus have manifestations similar to those produced by epithelial carcinomas in the same location; these typically include dysphonia, hoarseness, dysphagia, and cervical lymphadenopathy.¹⁶ The macroscopic appearance of laryngeal lymphoma is described as a smooth submucosal swelling or polypoid mass without ulceration, which may be a useful feature for endoscopic diagnosis.¹⁷ Substantial tissue quantity is necessary for specific histologic characterization. Immunohistochemistry can determine B-cell lineage, which demonstrates CD19, CD20, and CD22 immunoglobulins, or T-cell lineage, which demonstrates CD2 and CD3.¹⁸ NK-cell lymphoma, a rare subclassification of T-cell lymphoma with a poor prognosis, expresses the cell adhesion molecule CD56 and demonstrates an aggressive angiocentric growth pattern.¹⁹ Furthermore, cytogenetic and molecular studies can be performed to tailor the therapeutic approach.¹⁸ Because NHL is considered highly radiosensitive, the literature is supportive of radiation therapy as the treatment of choice for primary lesions with or without regional lymph node involvement.^2,12 However, in patients with more disseminated disease, a combination of radiation and chemotherapy is favored.^13,20

Previous reports have suggested a male predominance of laryngeal lymphoma^6,14; however, our study indicated a 2:1 female predominance, in keeping with the study of King et al.⁴ Additionally, two-thirds of reported primary laryngeal lymphoma was left-sided, with most tumors arising in the supraglottis, specifically the epiglottis and aryepiglottic folds.^5,21 Our study, however, identified no predilection for either side. It is likely that predispositions to one side or one sex are the result of statistical clustering in a particular series.

In our series, pretreatment imaging demonstrated that laryngeal lymphoma always involved the supraglottis and occasionally extended into the glottis and less frequently the subglottis. The tumor most frequently involved the false cords and aryepiglottic folds but was also frequently seen in the epiglottis and true cords. These findings are compatible with prior endoscopic reports, which documented a predilection for the epiglottis, aryepiglottic folds, and vestibule.^5,22,23

On pathologic evaluation, 90% of reported cases demonstrated a submucosal component, with only 10% being primarily mucosal in origin. Most interesting, the localized mucosal cases in our series were 2 of the 3 NK/T-cell lymphoma phenotypes, with the third NK/T-cell lymphoma phenotype demonstrating involvement of both the mucosa and submucosa. This supports a preference of NK/T cell lymphoma for the mucosa.¹⁵ Furthermore, the supraglottic and primarily submucosal location of laryngeal lymphoma is in keeping with prior radiographic imaging reported by Takayama et al²⁴ and King et al.⁴

Most reported cases of laryngeal lymphoma have been of the B-cell phenotype, with only a small percentage being of the NK/T-cell phenotype.^5,21,24 Our study was consistent with this finding, demonstrating a B-cell phenotype to NK/T-cell phenotype ratio of 6:1.²⁵ We found that the diffuse large B-cell lymphoma was the most common immunophenotype, consistent with prior reports,²⁵ followed by the MALT. As previously noted, the major imaging and pathologic distinction between the B-cell phenotype and the NK/T-cell phenotype was the involvement of the submucosa in all the cases with B-cell phenotype. Our findings suggest that the B-cell phenotype primarily affects the submucosa and secondarily involves the mucosa. This involvement is likely due to the aggregates of B-cell-specific lymphoid tissue within the submucosa of the larynx.¹⁵

In our series, most cases of laryngeal lymphoma demonstrated uniform moderate enhancement with intravenous contrast. The 2 cases that demonstrated heterogeneous enhancement were of the B-cell phenotype and did not otherwise illustrate a distinctive immunophenotype or other distinguishing feature. Lack of enhancement may also be seen in posttherapy CT, likely indicating treatment response.²⁶ There was no CT evidence of marked central necrosis or abnormal calcifications, features that might be useful for suggesting submucosal laryngeal lesions such as chondrosarcoma or other more aggressive neoplasms. Extralaryngeal tumor extension was most frequently noted to involve the hypopharynx and, less commonly, the oropharynx and strap muscles. However, 25% of cases were seen involving only the supraglottic larynx, indicating that laryngeal lymphoma does not always extend beyond the supraglottis as previously suggested.²¹ The extent of local spread is most likely related to the onset of symptoms and the time of imaging. However, the involvement of the strap muscles, tongue base, and oropharynx is of little diagnostic utility, because it is commonly seen with squamous cell carcinoma and is thus not a distinguishing feature. Cervical lymphadenopathy predominately involved the internal jugular chain and was seen in 20% of our cases in accordance with the previously reported value of 25%.⁵ This finding may be of diagnostic utility because cervical adenopathy is commonly seen in supraglottic squamous cell carcinoma. Lymphoma of the larynx, similar to lymphoma in other parts of the body, is metabolically active on PET-CT, a finding that may be of further utility in the future as molecular imaging continues to evolve.²⁷

MR imaging of laryngeal lymphoma demonstrated homogeneous intermediate T1-weighted and variable T2-weighted signal intensity and homogeneous gadolinium enhancement. The homogeneous signal-intensity characteristics of our lesions are consistent with the MR imaging of Fujita et al²⁸ and Takayama et al²⁴; however, heterogeneous intensity on T2-weighted and contrast-enhanced images has been reported by King et al.⁴ The variability in T2 signal intensity, as previously suggested, may represent the underlying cellularity of the tumor²⁸ and thus is likely to differ from lesion to lesion. However, MR signal-intensity characteristics are still diagnostically nonspecific, so the technique is primarily used for determination of the extent of tumor involvement.²⁸ Future use of diffusion-weighted imaging may improve specificity because lymphomas elsewhere show restricted diffusion compared with many other neoplasms.²⁹ Diffusion-weighted imaging was not performed in the cases included in our series.

In addition to squamous cell carcinoma and laryngeal lymphoma, there are other lesions that belong in the differential diagnosis of a uniformly enhancing mucosal or submucosal laryngeal mass. Paraganglioma, schwannoma, venolymphatic malformation, adenoid cystic carcinoma and other minor salivary tumors, rhabdomyosarcoma, chondrosarcoma, leiomyoma, spindle cell neoplasms, angiosarcoma, fibrosarcoma, enchondroma, tuberculoma, tracheobronchial papilloma, and rheumatoid arthritis should all be considered.