The Impact of the COVID-19 Pandemic on the Prognosis of Laryngeal Adenoid Cystic Carcinoma: A Case Report and a Literature Review

Abstract

Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a rapid deterioration with distant metastasis due to the COVID-19 pandemic is illustrated. Next, we present a literature review of this rare glottic ACC. The COVID-19 pandemic worsened the stage of presentation of many cancers and adversely affected their prognosis. The present case had a rapidly lethal course, undoubtedly due to the diagnosis delay caused by the COVID-19 pandemic, which impacted the prognosis of this rare glottic ACC. Strict follow-up is recommended for any suspicious clinical findings, as an early diagnosis will improve the disease prognosis, and to consider the influence of the COVID-19 pandemic, especially on the timing of common diagnostic and therapeutic procedures for oncological diseases. In the post-COVID-19 era, it is important to generate new diagnostic scenarios to achieve an increasingly rapid diagnosis of oncological diseases, especially the rare ones, through screening or similar procedures.

Keywords: COVID-19; adenoid cystic carcinoma (ACC); head and neck cancer; laryngeal adenoid cystic carcinoma (LACC); laryngectomy.

Figure 1

Endoscopic view of the larynx showing the lesion. The adenoid cystic carcinoma (ACC) arises from the minor salivary glands. It accounts for 1–5% of all head and neck malignancies. Since the minor salivary glands are present in small amounts throughout the larynx, the laryngeal adenoid cystic carcinoma is sporadic, representing less than 1% of all laryngeal malignancies [1]. Regarding the onset of laryngeal ACC (LACC), the prevalent age ranges from 50 to 60 years. However, younger generations can be affected, and both sexes are equally affected, with a slight male predominance and a male-to-female ratio of 1,5:1. There is no evidence connecting LACC etiology with smoking. An early perineural and hematological spread make this kind of carcinoma liable for local recurrence and distant metastasis, especially to the lung. Therefore, is important to increase the frequency of controls during follow-up [2]. Laryngeal ACC can originate from any part of the larynx. The most common origin is the subglottic area (64%), followed by the supraglottic area (25%), the glottic area (5%), and the trans-glottic area (6%) [3,4]. The clinical presentation is usually variable and related to the lesion location [5,6,7]. In November 2021, a 70-year-old no-smoker female patient presented to our hospital’s emergency department with stridor, severe dyspnea at rest, and hoarseness of voice. The O2 saturation level was 87% on air without cyanosis. An endoscopic laryngeal examination revealed bilateral vocal cord paralysis in adduction. Firstly, the patient underwent an urgent tracheostomy under general anesthesia. The procedure also included a laryngeal examination (micro-laryngeal surgery) under general anesthesia with tumor mapping, which revealed a bilateral mucosal thickening of the anterior thirds and anterior commissures of both vocal folds and a right vocal fold submucosal thickening (Figure 1). Multiple biopsies from different laryngeal areas were taken for histopathological examination. The pathological tissue revealed the presence of an adenoid cystic carcinoma of the solid type associated with the immunophenotype CK AE1 AE3 +, CD117+, CK7+/−, p63 +/−, p40+/−, Vimentin +/−, SMA+/−, S100+/−. Then, the patient underwent a CT scan of the neck chest and brain with a contrast medium and an abdominal ultrasound examination. The first chest, brain, and abdominal radiological evaluations did not show metastatic lesions. The neck CT scan revealed the presence of small submucosal bilateral glottic masses, associated with increased cervical lymph nodes volume, without subglottic and extra-laryngeal extensions (Figure 2).

Figure 2

CT scan showing (during hospitalization) pneumonia by Cytomegalovirus. At the lateral-basal segment of the right inferior lobe, in the subpleural level, the gross intraparenchymal collection with hydro-aerial content is compatible with the pneumatocele. In the lung window, multiple areas of parenchymal thickening are visible in the right basal location. (On the left, coronal section parenchymal window, on the right, axial section lung window). Partial laryngectomy (OPHL II B) with bilateral selective neck dissection (cervical nodal Robbins levels II–IV) and postoperative radiotherapy were planned to manage this case. Unfortunately, this planned surgical intervention was impossible because of the patient’s poor general conditions. Moreover, one of the follow-up CT scans of the chest (three months after the initial one) revealed the presence of bilateral diffuse multiple micronodules, which were considered early distant metastasis from the laryngeal adenoid cystic cancer (Figure 3).

Figure 3

CT scan windows showing metastasis and inflammatory phenomena on both sides of the lung. (On the left, axial parenchymal lung section. On the right, axial lung window). During hospitalization, bacterial pneumonia began, worsened by secondary viral (Cytomegalovirus) and fungal pneumonia. The patient received a triple antibiotics course with an antiviral, an antifungal, and systemic and local inhalational corticosteroids. However, despite the medical therapy, the chest condition deteriorated progressively (Figure 4).

Figure 4

CT scan on the left. The neck scan revealed the presence of small submucosal bilateral glottic masses, associated with increased cervical lymph node volume, without subglottic and extra laryngeal extensions. (A) Axial section basal CT scan on the left. (B) Axial contrast-enhanced CT on the right. Lung window showing a small scar at the level of the right lower lobe from previous pneumonia reported by the patient; (C) coronal and (D) axial lung window). Due to the worsening conditions, the patient was mechanically ventilated because of acute respiratory failure. Despite the therapy and mechanical ventilation, the pulmonary functions deteriorated progressively, resulting in the patient’s death. The patient was not diabetic, hypertensive, or cardiopathic and was not a smoker. By anamnestic clinical history, we discovered that two years before this event (October 2019), the subject presented mild hoarseness of voice. At the time, an endoscopic laryngeal examination revealed bilateral mobile vocal folds without apparent abnormalities. For further confirmation, the subject underwent a laryngeal exam under general anesthesia, which showed the absence of any macroscopic lesion, and the histopathological results of the biopsies were negative. The physicians scheduled a follow-up after three months, but unfortunately, the lockdown caused by the COVID-19 pandemic and the fear of viral infection prevented her to attend the recommended follow-up visits. The patient was COVID-19-negative throughout the whole illness (Table 1). We performed a literature analysis by searching the PubMed database for ‘laryngeal adenoid cystic carcinoma’. We did not limit the search to article types because of the rarity of the disease and the little number of papers about it. We choose only papers published in English within the past five years. The articles in the database whose full text could not be found were also excluded. The title and abstracts of the identified manuscripts were initially screened and selected by all authors independently (IF, AC, PGM, HE, RA, MF, MR, DM, AG, MdV, CB, and AM) based on their relevance to the review topic. The following set of shared chosen inclusion criteria was applied individually to the selected articles in their full-text version: primary laryngeal affection of adenoid cystic carcinoma and therapy consensus of LACC. The literature search yielded 48 papers. Subsequently, 28 studies were excluded because they did not meet the objective of our review, and 20 studies were included and discussed (Figure 5 and Table 2).

Figure 5

Articles selection on laryngeal adenoid cystic carcinoma. Primitive LACC is a rare head and neck carcinoma with slow growth but a high rate of malignancy due to its frequent perineural invasion. A high percentage of distant metastasis has been reported both at first diagnosis and during follow-up. The main distant metastasis site for LACC is the lung, but metastasis can develop in many sites. Iype et al. even described a case of an isolated scapular metastasis [8]. Although the first evaluation of neoplastic disease usually involves TNM staging according to AJCC, which is considered to have a significant prognostic value, Taha M. et al. observed that this is not true for LACC [9]. The histologic grade seems to be a more significant prognostic factor for survival in the presence of LACC, although this finding was established in a small sample of patients [10,11,12,13]. Radiation therapy is not considered a primary curative treatment for adenoid cystic carcinoma, whatever its location, but it has been widely used as an adjuvant treatment. Benefits in terms of local control and survival with adjuvant radiotherapy have been reported in many papers [13].