A Retrospective Study of Glottic Cyst Histopathology and Its Clinical Presentation

Abstract

To understand the frequency and clinical presentation of the four types of vocal-fold cyst described by the Koren classification. Glottic cysts operated in a 1-year period were grouped retrospectively into Koren A, B, C and D (KA, KB, KC, KD). The age and sex of the patient, cyst location, laterality, associated lesions, profession, daily water consumption, duration of symptoms prior to surgery and postoperative healing time were noted. Of 30 cysts, 14 KA, 10 KB, 4 KC and 2 KD were identified. Average age of symptoms in KA to KD was 45, 52, 40 and 37 years. KC and KD were found only in females unlike the male predominance of KA and KB. Striking zone was the location of 28/30 cysts with a focal pit in 1 KC and mucosal bridge in 1 KD. There was no significance to laterality or profession. Average daily water consumption was 1.8, 1.75, 2 and 2 L in KA to KD. Average duration of symptoms up-till surgery for KA to KD was 2.6 years, 1.4 years, 2.9 years and 1 month. Post-operative healing time for KA to KD was 6.6, 7.4, 11.7 and 10 weeks. KA was the commonest cyst excised followed by KB, KC and KD. The KD patients were earliest and youngest to present. All KC and KD cysts were found in females unlike the male predominance of KA and KB. As majority of the cysts were found on the striking zone, phonotrauma may be one of the etiologies for all four cysts.

Introduction

The diagnosis and management of benign glottic lesions has evolved, and become more precise, due to the advances made in diagnostic and therapeutic tools and our growing understanding of the pathophysiology of various laryngeal lesions. Vocal fold nodules, polyps and cysts are common benign glottic lesions, identified today typically using the stroboscopy light with high definition laryngoscopes. Histopathology has over the years revealed that vocal fold nodules are thickening of the basement membrane [1–3] unlike polyps and cysts, which are subepithelial lesions.

Shvero and Koren’s [4] research histopathologically identified four distinct types of subepithelial cysts where each cyst type has a distinctly different combination of capsular epithelium and content. Koren type A (KA) has a non-ciliated respiratory epithelium capsule with mucous content (Fig. 1) unlike Koren B (KB) type, which has a ciliated respiratory epithelium (Fig. 2). Both KA and KB cysts are described to have a similar positive histochemical staining of the lining epithelium with Alcian blue (AB) and periodic acid Schiff (PAS). The cyst wall of both Koren C (KC) and Koren D (KD) cysts is stratified squamous epithelium with a similar negative histochemical staining of the lining epithelium with AB and PAS. However the content is distinctly different with KC cysts (Fig. 3) revealing no keratin and only mucoid content, unlike the layers of keratin constituting the content of KD cysts (Fig. 4).

Fig. 1.

Koren A cyst with a cyst wall of respiratory non- ciliated epithelium and mucoid content, as seen on Haematoxylin-Eosin staining at 100 X magnification

Fig. 2.

Koren B cyst with a cyst wall of respiratory ciliated epithelium and mucoid content, as seen on Haematoxylin-Eosin staining at 100 X magnification

Fig. 3.

Koren C cyst with a cyst wall of stratified squamous epithelium and mucoid content, as seen on Haematoxylin-Eosin staining at 40X magnification

Fig. 4.

Koren D cyst with a keratinizing stratified squamous epithelium cyst wall and keratin content, as seen on Haematoxylin-Eosin staining at 40X magnification

Though phonotrauma is thought to be one of the primary etiologies of nodules, polyps and cysts [3, 5, 6] the clinical presentation and distribution pattern of each specific type of Koren cyst has not previously been published and may provide some answers to the pathophysiology and prognosis of each type of cyst. The objective of this study is to attempt to understand the clinical presentation and distribution pattern of these four distinct types of subepithelial vocal fold cysts.

Methods

This research has been granted institutional ethics clearance. This is a retrospective observational study performed at the voice and swallowing center of a tertiary care hospital. Glottic cysts operated in a 1-year period (2021–2022) were grouped into KA, KB, KC, and KD. All cysts had been operated upon by the author using a mini-microflap technique with a combination of cold steel and CO₂ acublade laser in superpulse, repeat mode at 10 Watts.

The detailed histopathology reports and images of the slides were retrieved from the database of the histopathology department. The age of symptom presentation, sex, cyst location, laterality, associated lesions, profession, daily water consumption, duration of vocal symptoms up till surgical intervention and time taken for healing following surgery, were noted retrospectively from medical records. Healing time was taken as the duration the patient was under ongoing voice therapy till voice stabilization was achieved. The medical records accessed were the voice clinic history sheets, stroboscopy reports, operative notes and histopathology slides and reports.

Results

Of a total 30 subepithelial vocal fold cysts, operated in a 1-year duration at our Voice Center, 14 KA, 10 KB, 4 KC and 2 KD cysts were noted. Average age of the patient at symptom presentation was 45 (24–60) years in KA cysts, 52 (32–80) years in KB cysts, 40 (4–64) years in KC cysts and 37 (30–43) years in KD cysts. All KC and KD cysts (100%) were found in females unlike the male predominance in KA cysts (10 males, 4 females) and KB cysts (6 males, 4 females).

All cysts, barring 2 KB cysts, were situated at the striking zone, which is the mid-membranous area of the true vocal fold (Fig. 5). These 2 KB cysts were found on the superior surface of the vocal fold, near the ventricle. An associated focal pit was found on the contralateral vocal fold of a KC cyst patient and an associated mucosal bridge was found on the contra-lateral vocal fold of a KD cyst patient.

Fig. 5.

Histopathologically proved Koren type A cyst seen on the striking zone of the left vocal fold on flexible laryngoscopy

Laterality revealed 8 right, 6 left KA cysts; 6 left, 4 right KB cysts; 3 right, 1 left KC cysts and 2 left KD cysts. A total of 19/29 patients were actively engaged in a profession or were students. Average daily water consumption in liters was 1.8, 1.75, 2 and 2 in KA, KB, KC and KD cysts respectively.

Average duration of vocal symptoms up till surgery was 2.6 years (4 months–12 years) in KA, 1.4 years (15 days–5 years) in KB, 2.9 years (7 months–7 years) in KC and 1 month (both patients) in KD. Average healing time in weeks following surgery was 6.6 (4–12) for KA, 7.4 (6–10) for KB, 11.7 (10–13) for KC and 10 (8–12) weeks for KD cyst patients.

Discussion

Monday et al. [7] in 1983 were the first to describe the special lining of vocal fold cysts, including squamous epithelium and cuboidal or columnar epithelium resembling respiratory epithelium, which are also often found together. Shvero and Koren’s [4] landmark study of 2000 has described four distinct types of vocal fold cysts, termed the Koren classification. Their study over a duration of 13 years revealed 22 KA, 4 KB, 8KC and 7 KD cysts in a total of 41 cysts.

In the current study of a total 30 cysts, operated upon in a one-year duration, 14 were KA, 10 KB, 4KC and 2 KD. Thus both the studies revealed KA type cyst to be the most commonly prevalent with 46.7% KA cysts noted in the present study as compared to 53.7% KA cysts noted by Shvero et al. In Shvero’s study the KB variant was least common unlike the current study where the KD variant was most uncommon.

The KC cyst may be considered to be an enigma as the cyst lining resembles a KD cyst, but the content of the cyst histologically resembles the KA and KB cyst. The possibility of a KC cyst developing due to metaplasia of the capsular mucosa of a KA or KB cyst should be considered and further researched upon. Monday et al’s [7] 1983 publication mentions two kinds of epidermoid cysts encountered, the true epidermoid cyst lined by normal malpighian epithelium and filled with keratin material and the epidermoid inclusion cyst consisting of a solid malpighian epidermoid formation without keratin, which may represent an earlier stage in the formation of the cyst but is not really a cyst in itself. This epidermoid inclusion cyst mentioned, may be similar to the KC cyst described by Shvero et al. [4].

In the current study KA and KB cysts were found predominantly in males (66.7%), KA cysts found in 71.4% males and KB cysts in 60% males. The average age at presentation was 45 and 52 years for KA and KB cyst patients respectively. These demographics of a male preponderance and the 4th–5th decade of presentation are similar to vocal fold polyp demographics, suggesting similar etiopathologic triggers in both these groups. Unlike the male predominance seen in KA and KB cysts, all KC and KD cysts, in the current study, were found in females with an average age of presentation of 40 and 37 years. However considering all 4 Koren cysts together, a male predominance (55.2%) was observed. Previous studies of laryngeal cysts have shown variable sex predominance with DeSanto et al. [8] finding an equal distribution between males and females, Kaur et al. [9] finding a male predominance and Newman et al. [10] finding a female predominance.

Of the 72 cases of cysts specifically of the vocal folds, observed by Martins et al. [11], 44 were females. Similarly Kirke at al [12]. found a female preponderance of glottic cysts though Nerurkar et al. [13] observed 60% male patients with vocal fold cysts in a 10-year retrospective study which is very similar to the Shvero et al. [4] study revealing a 61% male predominance.

There was no significance in laterality of the lesions or profession in the present study.

Different etiologies have been historically proposed for the development of mucous retention and epidermoid cysts which seems to be justified keeping in mind the distinctly different histopathology of these two broad groups of cysts.

A blockage of the duct of a seromucinous gland of the vocal fold is proposed as the primary etiology of a mucous retention cyst. This blockage may be due to persistent phonotrauma in terms of a hard glottal attack and vocal overuse. Lending support to the notion that vocal fold nodules, polyps, and cysts arise from vocal misuse, Andrade et al. [14] studied the prevalence of hard glottal attack in patients with vocal fold lesions and muscle tension dysphonia as compared with control subjects and discovered that the voice-disordered groups of patients demonstrated significantly higher frequencies of hard glottal attack than control subjects did. A study by Milutinovic et al. [15] revealed hyperkinetic pattern of speech by surface EMG revealing increased muscular activity during speech and phonation in patients of vocal fold cysts. Titze [16] has analyzed the stress forces on the vocal folds due to phonation and has determined that maximal impact stress occurs in the mid-membranous vocal fold.

The presence of 91.7% of mucous retention cysts on the striking zone (mid-membranous vocal fold) suggest the role of phonotrauma in this current study, which is similar to previous published studies [11, 13, 17, 18]. Phonotrauma may be responsible for thickened epithelium or edema blocking the seromucinous gland ducts [13].

In the current study two KB cysts (8.3%) were found on the superior surface near the ventricle and anatomical studies have revealed the preponderance of seromucinous glands on the false vocal fold and ventricle [19, 20].

Besides phonotrauma, decreased laryngeal hydration has been proposed as one of the possible factors responsible for the formation of mucous retention cysts [13]. The two types of hydration are systemic hydration, that refers to the fluid content within the body and vocal fold tissue and superficial or surface hydration which is the fluid lining the vocal fold surface and laryngeal lumen [21]. Thick laryngeal secretions due to decreased laryngeal hydration may plug the duct of a seromucinous gland with consequent mucous retention cyst formation. Systemic tissue hydration is vital to healthy vocal performance and, to some extent, self-perceived vocal effort [22]. Adequate hydration of the body is considered to be 2 L or eight glasses of water per day [23]. The average daily water consumption was 2 L in the KC and KD group and below 2 L in the KA and KB group in the current study.

The classically described epidermoid cyst lined by keratinized stratified squamous epithelium with keratin content is classified by the Shvero-Koren system as Koren type D (KD). The keratinized stratified squamous lining of this cyst suggests various etiologies of its development. One etiology proposed for epidermoid cysts is that they are the result of congenital anomalies occurring in the fourth and sixth branchial arch in the course of development of the larynx [7, 24, 25]. The younger age of presentation of the KC (one a 4 year old child) and KD cyst patients and the presence of associated lesions (sulcus and mucosal bridge), which are frequently considered congenital, both point towards a possible congenital etiology. The other proposed etiology is that epithelial tears develop, probably due to phonotrauma, and subsequent migration of epithelium into the SLP results in the formation of an epidermoid cyst [6, 7]. In our study 100% of KC and KD cysts were found on the striking zone suggesting phonotrauma as one of the etiological agents. The clinical significance of this finding is the role of pre and postoperative voice therapy in symptomatic cysts. The therapy is not only targeted to achieve optimal postoperative vocal outcomes, without wrong compensatory techniques, but also aimed at breaking the cycle of hard glottal attacks, possible muscle tension dysphonia and hyperkinetic speech pattern, which may have had an etiological role in the development of the cyst. With regard to postoperative care, most authors advocate a period of 4 to 14 days of absolute voice rest following vocal fold microsurgery [26]. All our post-operative cases of subepithelial cysts are advised a week of voice rest followed by relaxation voice therapy and adequate laryngeal hydration. A stroboscopy is performed at 1 month to guide the further plan of treatment by the voice therapist or surgeon, if indicated.

Shvero’s study [4] revealed the duration of hoarseness in cyst patients varying from 1 month to 5 years, with the current study noting duration of hoarseness from 1 month to 12 years. Specifically, the average duration of vocal symptoms up till surgical intervention was 2.6 years in KA, 1.4 years in KB, 2.9 years in KC and 1 month in KD. Thus the mucous retention cysts that revealed ciliated columnar mucosal lining (KB), had on an average, 1.2 years shorter duration of vocal symptoms compared to the KA cysts which had no identifiable cilia. This raises the question if long-term pressure by the contents of a cyst may cause pressure necrosis of any cilia that may have actually been present, thus converting a KB to a KA type of cyst.

The average healing time in weeks following surgery was 6.6 for KA, 7.4 for KB, 11.7 for KC and 10 weeks for KD. The average healing time taken for KA and KB cysts as a group was 6.9 weeks and for KC and KD cysts as a group was 11 weeks. The longest healing time following surgery was found in the KC group, with this group also presenting with the longest duration of symptoms averaging 2.9 years. However KD cysts, which had the shortest duration of symptoms averaging 1 month, did not have the quickest healing time, among the 4 cyst groups.

Because cyst excision requires substantial dissection within the lamina propria, the potential for scar is higher than in other benign lesions such as polyps or pseudocysts [12]. Though all our cysts were excised using a combination of both cold steel and CO₂ laser with the scanning system, the principles of phonomicrosurgery with maximum preservation of SLP and overlying epithelium were followed routinely. Benninger [27] in a randomized prospective trial compared cold dissection technique versus microspot CO₂ laser–assisted dissection for surgical treatment of benign laryngeal lesions. In this study of 37 patients, there was no difference in clinical outcomes measured by acoustic analysis, airflow rates, videostroboscopic, and audio perceptual analysis with either technique.

In a study by Benbouja and Hartnick [6], mucous-retention cysts appeared within the superficial lamina propria (SLP) as opposed to epidermoid cysts which were seen more deeply in the lamina propria, and similar observations were noted in cysts operated in the current study also, with KA and KB cysts found more superficially in the SLP, and KC and KD cysts present deeper in the SLP. Superficial lesions are likely to heal better than lesions deeper in the lamina propria [28] possibly due to increased levels of hyaluronic acid in the SLP. Furthermore, decorin is present in high concentration in the superficial layer of the lamina propria and the role of decorin in reducing fibrosis and scarring after injury is well documented in the dermatology literature [29]. Decorin is a short chain proteoglycan adhesive molecule found in the ECM that helps keep collagen fibrils uniformly parallel to each other. This may be another explanation for the faster healing of KA and KB cysts which tend to be found more superficially in the SLP, and longer healing time of KC and KD cysts which are often found deeper in the SLP.

A 20–40% of epidermoid cysts may have surrounding inflammatory reaction with the accumulation of lymphocytes and plasma cells, suggesting chronic inflammation, which may in turn decide the postoperative healing time and pattern [24]. All cysts had been operated using the Acublade CO₂ laser with optimal laser fluence parameters and previous research by Matar et al. [30] has concluded that this is a reliable tool that may be used in the excision of vocal fold cysts.

Thus the wound healing and remodeling of the SLP following phonomicrosurgery for subepithelial vocal fold cysts is probably multifactorial, with presence of surrounding inflammation, depth of the cyst within the SLP, duration of symptoms, size of the cyst and postoperative voice rest [26] and voice therapy all playing a role. Complete cyst excision is the treatment of choice for symptomatic vocal fold cysts and though this is associated with a good prognosis [31], the exact histopathological type may account for the varied healing patterns.

Limitations of this study are that a larger number of cysts studied, ideally in different geographical centers, would give a more accurate percentage of the four types of vocal fold cysts described. Cysts in this study were clinically documented on stroboscopy as subepithelial vocal fold cysts, and not specifically as mucous retention or epidermoid type. Thus the accuracy of the specific clinical diagnosis could not be ascertained.

Conclusion

KA was the commonest cyst excised (47%) followed by KB (33%), KC (13%) and KD (7%). The average age of presentation was the youngest in KD cyst patients who also presented the earliest. In this study, all KC and KD cysts were found in females, occasionally with associated lesions such as sulcus and mucosal bridge, unlike KA and KB cysts that showed a male predominance and no associated lesions. As 93% of the cysts were found on the striking zone, phonotrauma may be one of the etiologies for all types of cysts.

The longest healing time following surgery, was found in the KC group, with this group also presenting with the longest duration of symptoms, however KD cysts which had the shortest duration of symptoms, did not have the quickest healing time among the 4 cyst groups. As epidermoid cysts lie deeper in the SLP, this may be a possible explanation for the longer healing time of KC and KD cysts.

Declarations

Conflict of interest

There were no financial or non-financial interests that are directly or indirectly related to the work submitted for publication. There are no conflicts of interest to disclose.

Meeting Information

Poster presentation at the ALA meeting at COSM, Boston, 2023.