Lymphomas are a heterogeneous group of malignant tumors which are mainly composed of two major categories: Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). The subtypes of lymphoma can be divided into B-cell lymphomas, T-cell and natural killer-cell lymphomas (T/NK-NHL) and HL based on the cell of origin [3–5]. MALT-lymphoma and diffuse large B-cell lymphoma (DLBCL) mentioned in this paper are subtypes of non-Hodgkin lymphoma (NHL) stemming from marginal zone B-cells. Approximately 30% of NHLs show heterogeneous extra-nodal manifestations. Besides the gastrointestinal tract, head and neck is the second most frequently involved extranodal site in NHL. NHL of the head and neck mostly occurs within the Waldeyer’ ring, paranasal sinuses, salivary glands, thyroid gland and orbit. The larynx is a very rare site for NHL, and its incidence rate is less than 1% in all laryngeal tumors [6, 7]. The diffuse large B-cell lymphoma (DLBCL) and the MALT-lymphoma are the most common primary tumors of larynx originating from hematopoietic system [8, 9].
The presenting symptoms and signs of laryngeal lymphoma varied from site to site. The most common symptom was hoarseness (70.2%), followed by throat pain (26.3%), dyspnea (17.5%), and dysphagia (17.5%). B-symptoms (including night sweats, weight loss and fever) were rare (14.0%) [1]. In this study, all patients developed hoarseness without B symptoms. Indirect laryngoscopy often shows a polypoid submucosal mass without ulcer or other particular diagnostic characteristics. Two-thirds of the tumors tend to invade supraglottic regions, especially the epiglottis and aryepiglottic folds [10]. This is because the lesions mostly originate from the mucosa associated follicular lymphoid tissue in the lamina propria of the supraglottic region. NHL is speculated to originated from two parts of the larynx: 1) the special lymphoid tissue aggregates in submucosa, mainly B-cell line, or 2) mucosa-associated lymphoid tissues (MALT), mainly originated from the epiglottis and aryepiglottic folds [11].
Laryngeal lymphoma is usually characterized by submucosal mass in the supraglottic region, resulting in narrowing of the laryngeal cavity. The lesions may involve the glottic and subglottic areas downward, and the pharyngeal lymph ring may also be involved upward. In our series of study, imaging findings revealed that all the patients with laryngeal diffuse large B-cell lymphoma (DLBCL) had supraglottic and glottis involvement. The tumor most involved the false cords, aryepiglottic folds and true cords. In our other three cases of MALT-lymphoma, two cases were centered in the subglottic, involving the glottic region, resulting in laryngeal obstruction. One case was centered in the supraglottic region and involved the glottic region at the same time. This is not consistent with the imaging findings previously reported by Takayama et al and King et al that laryngeal lymphoma rarely originated from subglottic region [10, 12]. It may be because there were too few MALT-lymphomas in their cases of study. It was not surprising that NHL of larynx were not restricted to the glottis in our cases, because lymphatis were very scarce in the true vocal cords. As showed in our cases of study, glottic tumors were often secondary to the spread of tumor tissues in adjacent areas. Among the seven reported cases of B-cell lymphomas causing laryngeal stenosis, five cases were MALT-lymphoma located in the subglottic region [13–19]. This is consistent with the results of our study, which may indicate that most of the NHL located in the subglottic region and causing laryngeal stenosis are MALT-lymphoma.
Compared with the pathological classification and image morphological characteristics, diffuse large B-cell lymphoma (DBLCL) and MALT-lymphoma showed mass formation at corresponding sites. One case of diffuse large B-cell lymphoma (DBLCL) extended to the hypopharynx, and one case of MALT-lymphoma had the same type of lesions in the orbit, and this extensive involvement should raise the suspicion of lymphoma. Because of its submucosal origin, the surface of the lesions is mostly smooth [7, 12, 20]. In all of our enhanced MRI images, the smooth surface of the tumor was observed with more obvious linear enhancement of the mucosa. On CT plain scan, the lesions showed homogeneous and medium density similar to muscle tissue, and moderate homogeneous enhancement was found on contrast-enhanced scan. No obvious cystic degeneration, necrosis, calcification and cartilage destruction were the typical features. The results showed that the high signal intensity of laryngeal NHL on T1WI was homogeneous or slightly lower than that of muscle, while on T2WI it was inhomogeneous and slightly hyperintense. The mucosal layer with high signal intensity on enhanced T1WI was clearly displayed and continuously smoothed, indicating that the lesion originated from submucosa [10]. In this study, diffuse large B-cell lymphoma (DBLCL) was more prone to had cervical lymphadenopathy than MALT-lymphoma. The density, signal intensity and enhancement of the enlarged lymph nodes were consistent with those of the primary lesions, which were also confirmed in the literatures of NHL in other parts of the head and neck [20, 21].
The imaging findings of laryngeal NHL are easy to be confused with other laryngeal lesions. Due to the lack of research on imaging manifestations of this disease, all the above five cases were misdiagnosed as squamous cell carcinoma at the initial diagnosis, and the diagnostic coincidence rate was low. Laryngeal squamous cell carcinoma (LSCC) originated from the mucous layer. The surface of the lesion was not smooth. It showed uneven moderate or significant enhancement on enhanced scan. It was easy to invade laryngeal cartilage. The primary lesion and enlarged lymph nodes were mostly accompanied with necrosis and showed ring enhancement [22]. Besides lymphoma and squamous cell carcinoma, it is also necessary to differentiate them from other laryngeal masses located in the mucosal or submucosal with homogeneous enhancement[12]. Neuroendocrine tumor-atipical carcinoid, paraganglioma, schwannoma, adenoid cystic carcinoma and other minor salivary tumors, sarcoma, tuberculoma, tumor-like lesions (Brown tumor and inflammatory myofibroblastic tumor), and inflammatory lesions should all be considered [23].
With the progress of MRI technology, DWI, ADC and dynamic contrast-enhanced MRI (DCE-MRI) are more and more used in the diagnosis and differential diagnosis of head and neck lymphoma [24, 25]. Based on the principle of different attenuation coefficient of the same material under different X-ray energy, Dual-Energy CT (DECT) collect data at the same time with high and low energy scanning scheme, and obtains iodine based image, water-based image, energy spectrum curve and virtual plain scan image by post-processing methods such as material separation and reconstruction technology. In addition, the parameters such as iodine concentration, overlay value and slope of energy spectrum curve obtained can provide additional information for disease identification. Seidler et al. has shown that machine learning assisted-DECT texture analysis can distinguish metastatic lymph nodes of head and neck squamous cell carcinoma from lymphoma, normal lymph nodes, or inflammatory [26]. Perhaps these techniques may be helpful in differentiating NHL from other laryngeal lesions.