Abstract

Metastases to the larynx from distant primary malignancies are quite rare, but they should be considered in the differential diagnosis of submucosal laryngeal lesions. An 80-year-old male presented to our clinic with complaints of productive cough and hoarseness. Videolaryngoscopy revealed submucosal fullness in the right hemilarynx, pushing the right band ventricle mucosa medially and causing evident narrowing of the airway. Histopathological evaluation and immunohistochemical staining of the endolaryngeal submucosal biopsy specimen, obtained from the right ventricular fold, was diagnosed as laryngeal metastasis of prostate adenocarcinoma. This case is presented due to the scarcity of laryngeal metastases from prostate adenocarcinoma and is discussed in the context of literature.

Introduction

Prostate carcinoma is known as the most prevalent malignancy affecting the male population. Metastatic lesions from prostate adenocarcinoma are reported at different rates according to their histopathological subtypes. The most common (7-40%) distant metastases are bone metastasis, while head and neck metastases of prostate cancer are uncommon (1). Metastases to the larynx from distant sites are most commonly caused by tumors such as malignant melanoma and renal adenocarcinoma while reported laryngeal metastases of prostate adenocarcinoma are uncommon (2, 3). In this report, we present a case who presented to our clinic with hoarseness, productive and persistent cough complaints and was diagnosed with metastatic prostate adenocarcinoma to the larynx.

Case Report

An 80-year-old male patient without significant comorbidities was initially followed for benign prostatic hyperplasia and underwent a prostate biopsy, which was reported as Gleason score 7 prostate adenocarcinoma.

During the same time interval, he was evaluated at another otolaryngology department because of hoarseness and cough starting after a recent upper respiratory tract infection. After clinical evaluation, due to the persistence of widespread edematous appearance in endolaryngeal structures, microlaryngoscopy and biopsy were performed. The histopathological evaluation of the biopsy was reported as edematous mucosa without further specific findings.

As there were no signs of improvement, the patient presented to our clinic for further evaluation. During the ear, nose, and throat examination, a 1.5 cm, hard and palpable lymphadenopathy was identified at level three of the right side of the neck; and a submucosal fullness in the right hemilarynx, pushing the right band ventricle mucosa medially; evident narrowing of the airway was also observed during videolaryngoscopy. Computed tomographic images demonstrated a locally invasive mass lesion with partial destruction of the thyroid cartilage and obliteration of the right pyriform sinus (Figures 1 and 2).

Microlaryngoscopy was performed under general anesthesia and numerous deep-located biopsies were taken from the indurated submucosal mass lesion after incising the right band ventricle mucosa (Figure 3). Histopathological and immunohistochemical evaluation of the biopsy samples revealed prostate-specific acid phosphatase (PSAP) and cytokeratin 5/6 negative, and prostate-specific antigen (PSA) positive high grade epithelial malignant tumor consistent with metastatic prostate adenocarcinoma (Figures 4 and 5). Gallium-68 prostate-specific membrane antigen positron emission tomography-computed tomography (PET/CT) identified the primary lesion in the prostate left lobe and widespread metastases in the right hemilarynx, right cervical level II and left cervical level VB lymph nodes and bony structures (left clavicle, vertebrae C3-T10-L4, bilateral pelvis, sacroiliac joint, anterolateral fifth and sixth costa). Lumbosacral CT findings also revealed sclerotic metastatic foci in the vertebrae, which are also consistent with the metastatic prostate carcinoma.

The patient was discussed by the Dokuz Eylül University-Head and Neck Cancer Group and hormone therapy with androgen-deprivation therapy (ADT) was initiated. ADT had a significant impact on the patient’s laryngeal findings and a near-complete response was achieved (Figures 6 and 7). The patient survived for 42 months after diagnosis and eventually died of distant metastases’ progression during the follow-up period. Informed consent was obtained from the patient for publication.

Discussion

Prostate carcinoma is the most common malignancy in men and a significant cause of cancer-related mortality following lung carcinomas (1). Prostate carcinoma metastases mostly target regionally the lymph nodes and distantly the bones (7-40%), particularly the vertebrae. Head and neck metastases are relatively uncommon (1.5%). Although larynx metastases are very rare, the most common metastatic locations among head and neck sites are the brain, the dura and the supraclavicular lymph nodes (3-6).

Majority of distant laryngeal metastases arise from malignant melanoma, renal cell carcinoma, and carcinomas of the breast, lung, and colon. Only six per cent of laryngeal metastases originate from prostate carcinoma (1, 2, 7). Although laryngeal metastases of distant organ malignancies are uncommon due to the cartilaginous structure of the larynx skeleton, age-related ossification of the laryngeal cartilage may increase the risk of metastasis (3). Prescher et al. (2) reported that a very high incidence (97%) of bone metastases was observed in an autopsy series of patients with advanced prostate carcinoma. Theories put forth on the pathophysiology of laryngeal metastases due to prostate carcinoma in the same study were the unification of micrometastases to the hematopoietic region of the ossified cartilage and the invasion of the cartilage lamina or its spread between the perichondrium/periosteum and the laryngeal skeleton. Consequently, these tumors developing in the area far from the laryngeal lumen tend to cause late symptoms (3, 8).

Although the clinical course of larynx metastasis of prostate cancer is mostly asymptomatic in the early period, in literature, voice changes at later stages are reported as the most common clinical complaint. Our case also presented with hoarseness as the initial symptom, which is consistent with the literature; however, cough which was not reported before, was also a symptom (1, 8).

Cross-sectional imaging techniques like CT, magnetic resonance imaging, and PET/CT are useful for diagnosis, but the definitive diagnosis is made by histopathological and appropriate immunohistochemical evaluation with PSA and PSAP. Although NKX3.1 immunohistochemical staining is highly sensitive for detecting metastatic prostate adenocarcinoma, it hadn’t been used in our patient’s diagnostic work-up (9).

A review conducted by van der Toom et al. (10) stated that PSA was not expressed in 5-10% of metastatic prostatic carcinomas and PSAP was not expressed in 16-23%.

ADT has considerably extended the expected lifespan of advanced prostate carcinoma patients. In addition, palliative radiotherapy is used in patients with distant bone metastases, particularly those involving the vertebrae. Also, laryngectomy is proposed as an option in patients with solitary laryngeal metastasis (3).

In our patient, ADT caused an almost complete structural response to laryngeal metastasis, with complete resolution of the patient’s laryngeal symptoms, and afterwards, it was possible to control the progression of vertebral metastases with external beam radiotherapy. Although the patient died of distant metastasis after 42 months during the follow-up period, the patient’s quality of life was considerably increased due to control of laryngeal metastasis and preservation of laryngeal functions with ADT and avoidance of tracheotomy until his demise.

Conclusion

In summary, metastasis from distant sites should always be kept in mind in the differential diagnosis of laryngeal submucosal lesions presenting with voice disturbances, difficulty in breathing, stridor or cough; especially in patients with a history of malignancy. Correct sampling with incision of the mucosa and obtaining adequate submucosal tissue samples is a prerequisite for precise diagnosis. Histopathological evaluation with appropriate immunohistochemical staining is a key factor for definitive diagnosis. As represented in our case, laryngeal metastasis of prostate adenocarcinomas may yield an excellent response to ADT, and it should be the first line of treatment modality when considering more invasive options such as laryngectomy and even tracheotomy.