Case Report
Laryngeal metastasis from lung cancer Umasankar Kalai, Karan Madan, Deepali Jain1, Anant Mohan, Randeep Guleria Departments of Pulmonary Medicine and Sleep Disorders and 1Pathology, All India Institute of Medical Sciences, New Delhi, India
ABSTRACT Metastatic tumors of the larynx are rare. The most common tumors metastasizing to the larynx are melanoma and renal cell carcinoma. Bronchogenic carcinoma metastasizing to the larynx has been rarely described. Herein, we report the case of a 49‑year‑old, chronic smoker, who incidentally had a laryngeal growth detected during flexible bronchoscopy examination for evaluation of suspected lung cancer. Histopathological examination of the laryngeal nodule and the biopsy obtained from the main bronchus growth confirmed the diagnosis of metastatic squamous cell carcinoma to the larynx from primary lung cancer. KEY WORDS: Carcinoma, laryngeal neoplasms, lung cancer, metastasis, squamous cell Address for correspondence: Dr. Anant Mohan, Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, Ansari Nagar, New Delhi ‑ 110 029, India. E‑mail: [email protected]
INTRODUCTION Metastatic tumors of the larynx are uncommon and may pose a diagnostic challenge, especially when the laryngeal lesion is the sole clinical manifestation. These tumors may remain clinically silent even in the presence of disseminated primary malignancy or uncommonly may be the primary clinical manifestation. Laryngeal infiltration from tumors arising in the nearby head and neck structures is well known and has been described. However, metastatic tumors to the larynx from other primary sites (secondary laryngeal tumors) are uncommon and account for less than 1% of all laryngeal tumors.[1]
CASE REPORT A 49‑year‑old male farmer presented with a history of fever, shortness of breath, and streaky hemoptysis for a duration of six months. He reported loss of appetite and weight loss of six kilograms over the last three months. He was taking antitubercular medications for two months from another center, based on the chest X‑ray abnormality, without Access this article online Quick Response Code:
Website: www.lungindia.com DOI: 10.4103/0970-2113.156249
268
any improvement in his symptoms. The sputum smear examination for acid fast bacilli (AFB) had been negative on three occasions previously. He was a chronic smoker with a 30‑pack‑year history of smoking. He denied a history of chest pain, change in voice or dysphagia. On clinical examination, the pulse rate was 84/minute, respiratory rate 16 breaths/minute, and there was no peripheral lymph node enlargement. The rest of the general physical examination was unremarkable. On examination of the respiratory system, the trachea was central, there was a stony dull note to percussion on the left hemithorax, and breath sounds were absent on the left side. Chest radiographs demonstrated an opaque, white left hemithorax without any shift of the trachea [Figure 1, Left Panel]. Contrast‑enhanced computed tomography (CECT) examination of the thorax [Figure 1, Right Panel] revealed a massive pleural effusion on the left side, with pleural nodularity, as well as subcarinal and right paratracheal lymph node enlargement. Diagnostic thoracentesis revealed a hemorrhagic pleural fluid, exudative, with low adenosine deaminase (ADA) levels (12 U/L). Three cytological examinations were negative for malignant cells. A flexible bronchoscopy examination revealed a small nodule (5 × 5 mm) on the inferior surface of the epiglottis, just above the anterior commissure of the vocal cord [Figure 2, Left Panel]. The left main stem bronchus was completely occluded by an exophytic endobronchial growth (approximately 1.5 cm × 1.5 cm). Histopathological examination of the biopsy from both the laryngeal nodule [Figure 2, Middle Panel] and the Lung India • Vol 32 • Issue 3 • May - Jun 2015
Kalai, et al.: Laryngeal metastasis from lung cancer
endobronchial growth demonstrated squamous cell carcinoma (moderately differentiated) [Figure 2, Right Panel]. An immunohistochemical examination for TTF‑1 (thyroid transcription factor 1) expression was negative on both the histopathological specimens. Keeping a diagnosis of non‑small cell (squamous) carcinoma of the lung (Stage IV), with asymptomatic laryngeal metastasis, treatment was initiated with platinum‑based doublet chemotherapy (Paclitaxel with Cisplatin) in view of the metastatic disease. No specific intervention was performed for the laryngeal nodule. However, the patient declined further chemotherapy following two cycles of chemotherapy and was lost to follow‑up.
DISCUSSION Ferlito et al., in 1993, reported 134 cases of secondary/ metastatic laryngeal tumors.[1] The most common primary site in metastatic laryngeal tumors was malignant melanoma followed by renal cell carcinoma.[2] The other reported sites included the breast, lung, prostate, colon, stomach, and ovary. Laryngeal metastasis from lung cancer is rarely described. Till the year 1996, only 16 cases of metastatic laryngeal tumors from primary lung cancer had been reported.[2] Larynx is a terminally located organ with regard to lymphatic and vascular circulation.[3] This fact likely explains why it is a rare site of metastases from tumors at other primary sites. The supraglottic and subglottic regions are the common locations for laryngeal metastases,
Figure 1: (Left panel) Chest radiograph showing a complete opaque left hemithorax, without any contralateral shift of the trachea. (Right panel) CT of the thorax demonstrating a large left pleural effusion with collapse of the underlying left lung
as these sites have a rich lymphatic and vascular supply. In our patient, the location of the metastatic laryngeal nodule was supraglottic. The pathway for primary pulmonary tumor metastasis to the larynx could be either hematogenous or via lymphatics. A hematogenous spread may occur in an orderly fashion from the right heart to the left heart, coursing through the aorta and external carotid artery before eventually reaching the larynx through the upper thyroid artery and upper laryngeal artery. A retrograde route is also possible via the vertebral venous plexus.[1] Retrograde lymphatic spread to the supraglottic larynx from the thoracic duct can occur via the left supraclavicular and internal jugular chain nodes. There are lymphatic vascular interconnections of the lymphatics of the supraglottic space, which communicate with the superior laryngeal vessels.[4] Signs and symptoms of metastatic laryngeal tumors do not differ from primary laryngeal tumors and vary according to the site and the size of involvement. Large‑sized lesions can lead to significant upper airway obstruction. Our patient was asymptomatic for the laryngeal growth and it was incidentally detected during bronchoscopy. This finding highlights the importance of performing a flexible bronchoscopy examination in patients with lung cancer as part of the staging evaluation, as it enables identification of radiologically normal sites of malignant involvement, as in our patient. Metastasis from bronchogenic carcinoma can be clinically silent or may be the presenting manifestation.[5] No other site of metastasis has been detected in the present case on the CECT scan of the thorax and abdomen. A positron emission tomography (PET) computed tomography (CT) scan was not performed in view of the advanced nature of the disease and no surgical intervention was being contemplated. Patients with lung cancer, especially the small cell variant, can have small asymptomatic primary tumors that can be associated with extensive symptomatic systemic metastatic involvement.[6] Patients with metastatic involvement of the larynx usually have a poor prognosis, as involvement of the larynx might be a pointer toward widespread lymphohematogenous dissemination. No specific management is required in patients with asymptomatic laryngeal involvement. Palliative laser resection of the metastatic laryngeal growth has been attempted, to treat symptomatic airway
Figure 2: (Left panel) Flexible bronchoscopy image showing the presence of a nodular supraglottic growth on the inferior surface of the epiglottis, just above the normal glottic opening. Histopathological examination of the bronchoscopic biopsy obtained from the laryngeal (middle panel) and main bronchus growth (right panel) confirms the diagnosis of squamous cell carcinoma (Hematoxylin and Eosin ×100) Lung India • Vol 32 • Issue 3 • May - Jun 2015 269
Kalai, et al.: Laryngeal metastasis from lung cancer
obstruction, with minimal morbidity.[7] In some patients with significant laryngeal obstruction, tracheostomy may also be required.[8] In our patient, similar to the previously published cases, lung cancer as the primary site was considered based on the clinical presentation and supporting radiological features. The limitation of immunohistochemistry in this setting is that the TTF‑1 positivity is found in only about 7 – 10% of the squamous cell carcinoma of the lung and the same is negative in head and neck carcinoma.[9] There are no reliable immunochemistry markers or histopathological features to differentiate the primary and metastatic sites in metastatic squamous cell carcinoma, wherein the involved sites are the head and neck region and the lung. To ascertain the nature and origin of a particular tumor by immunohistochemistry, application of a series of markers are usually required. Although a marker may occasionally be positive in a certain neoplasm (e.g. TTF‑1 in 1.53% of the cases of squamous cell carcinoma originating from the lung), it is the combination of different markers that confers the final diagnosis, along with the morphology. Although markers like CK 5/6, low MW cytokeratins, p63, and desmocollin‑3 may sometimes be useful to ascertain the nature and origin of the tumor, they have not been applied in the present case because they are less suitable to determine the site or non‑availability.[10] In such circumstances, diagnosis of the primary site is based on the clinicoradiological features only.
270
REFERENCES 1.
Ferlito A, Caruso G, Recher G. Secondary laryngeal tumors. Report of seven cases with review of the literature.Arch Otolaryngol Head Neck Surg 1988;114:635‑9. 2. Nicolai P, Puxeddu R, Cappiello J, Peretti G, Battocchio S, Facchetti F, et al. Metastatic neoplasms to the larynx: Report of three cases. Laryngoscope 1996;106:851‑5. 3. Quinn FBJr, McCabe BF. Laryngeal metastases from malignant tumors in distant organs. Ann OtolRhinol Laryngol1957;66:139‑43. 4. Bernáldez R, Toledano A, Alvarez J, Gavilán J. Pulmonary carcinoma metastatic to the larynx. J Laryngol Otol1994;108:898‑901. 5. Singh N, Madan K, Aggarwal AN, Das A. Symptomatic large bilateral adrenal metastases at presentation in small‑cell lung cancer: A case report and review of the literature. J Thorac Dis2013;5:E83‑6. 6. Madan K, Singh N. Small cell, large liver. BMJ Case Rep2012;2012. pii: bcr2012007650. 7. Morgan AH, Norris JW, Hicks JN. Palliative laser surgery for melanoma metastatic to the larynx: Report of two cases. Laryngoscope 1985;95:794‑7. 8. Koltsidopoulos P, Skoulakis C. Metastatic amelanotic melanoma of larynx‑hypopharynx. Otolaryngol Head Neck Surg 2011;144:125‑6. 9. Jagirdar J. Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung. Arch Pathol Lab Med 2008;132:384‑96. 10. Warth A, Muley T, Herpel E, Meister M, Herth FJ, Schirmacher P, et al. Large‑scale comparative analyses of immunomarkers for diagnostic subtyping of non‑small‑cell lung cancer biopsies. Histopathology 2012;61:1017‑25.
How to cite this article: Kalai U, Madan K, Jain D, Mohan A, Guleria R. Laryngeal metastasis from lung cancer. Lung India 2015;32:268-70. Source of Support: Nil, Conflict of Interest: None declared.
Lung India • Vol 32 • Issue 3 • May - Jun 2015
Copyright of Lung India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Laryngeal metastasis from lung cancer Umasankar Kalai, Karan Madan, Deepali Jain1, Anant Mohan, Randeep Guleria Departments of Pulmonary Medicine and Sleep Disorders and 1Pathology, All India Institute of Medical Sciences, New Delhi, India
ABSTRACT Metastatic tumors of the larynx are rare. The most common tumors metastasizing to the larynx are melanoma and renal cell carcinoma. Bronchogenic carcinoma metastasizing to the larynx has been rarely described. Herein, we report the case of a 49‑year‑old, chronic smoker, who incidentally had a laryngeal growth detected during flexible bronchoscopy examination for evaluation of suspected lung cancer. Histopathological examination of the laryngeal nodule and the biopsy obtained from the main bronchus growth confirmed the diagnosis of metastatic squamous cell carcinoma to the larynx from primary lung cancer. KEY WORDS: Carcinoma, laryngeal neoplasms, lung cancer, metastasis, squamous cell Address for correspondence: Dr. Anant Mohan, Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, Ansari Nagar, New Delhi ‑ 110 029, India. E‑mail: [email protected]
INTRODUCTION Metastatic tumors of the larynx are uncommon and may pose a diagnostic challenge, especially when the laryngeal lesion is the sole clinical manifestation. These tumors may remain clinically silent even in the presence of disseminated primary malignancy or uncommonly may be the primary clinical manifestation. Laryngeal infiltration from tumors arising in the nearby head and neck structures is well known and has been described. However, metastatic tumors to the larynx from other primary sites (secondary laryngeal tumors) are uncommon and account for less than 1% of all laryngeal tumors.[1]
CASE REPORT A 49‑year‑old male farmer presented with a history of fever, shortness of breath, and streaky hemoptysis for a duration of six months. He reported loss of appetite and weight loss of six kilograms over the last three months. He was taking antitubercular medications for two months from another center, based on the chest X‑ray abnormality, without Access this article online Quick Response Code:
Website: www.lungindia.com DOI: 10.4103/0970-2113.156249
268
any improvement in his symptoms. The sputum smear examination for acid fast bacilli (AFB) had been negative on three occasions previously. He was a chronic smoker with a 30‑pack‑year history of smoking. He denied a history of chest pain, change in voice or dysphagia. On clinical examination, the pulse rate was 84/minute, respiratory rate 16 breaths/minute, and there was no peripheral lymph node enlargement. The rest of the general physical examination was unremarkable. On examination of the respiratory system, the trachea was central, there was a stony dull note to percussion on the left hemithorax, and breath sounds were absent on the left side. Chest radiographs demonstrated an opaque, white left hemithorax without any shift of the trachea [Figure 1, Left Panel]. Contrast‑enhanced computed tomography (CECT) examination of the thorax [Figure 1, Right Panel] revealed a massive pleural effusion on the left side, with pleural nodularity, as well as subcarinal and right paratracheal lymph node enlargement. Diagnostic thoracentesis revealed a hemorrhagic pleural fluid, exudative, with low adenosine deaminase (ADA) levels (12 U/L). Three cytological examinations were negative for malignant cells. A flexible bronchoscopy examination revealed a small nodule (5 × 5 mm) on the inferior surface of the epiglottis, just above the anterior commissure of the vocal cord [Figure 2, Left Panel]. The left main stem bronchus was completely occluded by an exophytic endobronchial growth (approximately 1.5 cm × 1.5 cm). Histopathological examination of the biopsy from both the laryngeal nodule [Figure 2, Middle Panel] and the Lung India • Vol 32 • Issue 3 • May - Jun 2015
Kalai, et al.: Laryngeal metastasis from lung cancer
endobronchial growth demonstrated squamous cell carcinoma (moderately differentiated) [Figure 2, Right Panel]. An immunohistochemical examination for TTF‑1 (thyroid transcription factor 1) expression was negative on both the histopathological specimens. Keeping a diagnosis of non‑small cell (squamous) carcinoma of the lung (Stage IV), with asymptomatic laryngeal metastasis, treatment was initiated with platinum‑based doublet chemotherapy (Paclitaxel with Cisplatin) in view of the metastatic disease. No specific intervention was performed for the laryngeal nodule. However, the patient declined further chemotherapy following two cycles of chemotherapy and was lost to follow‑up.
DISCUSSION Ferlito et al., in 1993, reported 134 cases of secondary/ metastatic laryngeal tumors.[1] The most common primary site in metastatic laryngeal tumors was malignant melanoma followed by renal cell carcinoma.[2] The other reported sites included the breast, lung, prostate, colon, stomach, and ovary. Laryngeal metastasis from lung cancer is rarely described. Till the year 1996, only 16 cases of metastatic laryngeal tumors from primary lung cancer had been reported.[2] Larynx is a terminally located organ with regard to lymphatic and vascular circulation.[3] This fact likely explains why it is a rare site of metastases from tumors at other primary sites. The supraglottic and subglottic regions are the common locations for laryngeal metastases,
Figure 1: (Left panel) Chest radiograph showing a complete opaque left hemithorax, without any contralateral shift of the trachea. (Right panel) CT of the thorax demonstrating a large left pleural effusion with collapse of the underlying left lung
as these sites have a rich lymphatic and vascular supply. In our patient, the location of the metastatic laryngeal nodule was supraglottic. The pathway for primary pulmonary tumor metastasis to the larynx could be either hematogenous or via lymphatics. A hematogenous spread may occur in an orderly fashion from the right heart to the left heart, coursing through the aorta and external carotid artery before eventually reaching the larynx through the upper thyroid artery and upper laryngeal artery. A retrograde route is also possible via the vertebral venous plexus.[1] Retrograde lymphatic spread to the supraglottic larynx from the thoracic duct can occur via the left supraclavicular and internal jugular chain nodes. There are lymphatic vascular interconnections of the lymphatics of the supraglottic space, which communicate with the superior laryngeal vessels.[4] Signs and symptoms of metastatic laryngeal tumors do not differ from primary laryngeal tumors and vary according to the site and the size of involvement. Large‑sized lesions can lead to significant upper airway obstruction. Our patient was asymptomatic for the laryngeal growth and it was incidentally detected during bronchoscopy. This finding highlights the importance of performing a flexible bronchoscopy examination in patients with lung cancer as part of the staging evaluation, as it enables identification of radiologically normal sites of malignant involvement, as in our patient. Metastasis from bronchogenic carcinoma can be clinically silent or may be the presenting manifestation.[5] No other site of metastasis has been detected in the present case on the CECT scan of the thorax and abdomen. A positron emission tomography (PET) computed tomography (CT) scan was not performed in view of the advanced nature of the disease and no surgical intervention was being contemplated. Patients with lung cancer, especially the small cell variant, can have small asymptomatic primary tumors that can be associated with extensive symptomatic systemic metastatic involvement.[6] Patients with metastatic involvement of the larynx usually have a poor prognosis, as involvement of the larynx might be a pointer toward widespread lymphohematogenous dissemination. No specific management is required in patients with asymptomatic laryngeal involvement. Palliative laser resection of the metastatic laryngeal growth has been attempted, to treat symptomatic airway
Figure 2: (Left panel) Flexible bronchoscopy image showing the presence of a nodular supraglottic growth on the inferior surface of the epiglottis, just above the normal glottic opening. Histopathological examination of the bronchoscopic biopsy obtained from the laryngeal (middle panel) and main bronchus growth (right panel) confirms the diagnosis of squamous cell carcinoma (Hematoxylin and Eosin ×100) Lung India • Vol 32 • Issue 3 • May - Jun 2015 269
Kalai, et al.: Laryngeal metastasis from lung cancer
obstruction, with minimal morbidity.[7] In some patients with significant laryngeal obstruction, tracheostomy may also be required.[8] In our patient, similar to the previously published cases, lung cancer as the primary site was considered based on the clinical presentation and supporting radiological features. The limitation of immunohistochemistry in this setting is that the TTF‑1 positivity is found in only about 7 – 10% of the squamous cell carcinoma of the lung and the same is negative in head and neck carcinoma.[9] There are no reliable immunochemistry markers or histopathological features to differentiate the primary and metastatic sites in metastatic squamous cell carcinoma, wherein the involved sites are the head and neck region and the lung. To ascertain the nature and origin of a particular tumor by immunohistochemistry, application of a series of markers are usually required. Although a marker may occasionally be positive in a certain neoplasm (e.g. TTF‑1 in 1.53% of the cases of squamous cell carcinoma originating from the lung), it is the combination of different markers that confers the final diagnosis, along with the morphology. Although markers like CK 5/6, low MW cytokeratins, p63, and desmocollin‑3 may sometimes be useful to ascertain the nature and origin of the tumor, they have not been applied in the present case because they are less suitable to determine the site or non‑availability.[10] In such circumstances, diagnosis of the primary site is based on the clinicoradiological features only.
270
REFERENCES 1.
Ferlito A, Caruso G, Recher G. Secondary laryngeal tumors. Report of seven cases with review of the literature.Arch Otolaryngol Head Neck Surg 1988;114:635‑9. 2. Nicolai P, Puxeddu R, Cappiello J, Peretti G, Battocchio S, Facchetti F, et al. Metastatic neoplasms to the larynx: Report of three cases. Laryngoscope 1996;106:851‑5. 3. Quinn FBJr, McCabe BF. Laryngeal metastases from malignant tumors in distant organs. Ann OtolRhinol Laryngol1957;66:139‑43. 4. Bernáldez R, Toledano A, Alvarez J, Gavilán J. Pulmonary carcinoma metastatic to the larynx. J Laryngol Otol1994;108:898‑901. 5. Singh N, Madan K, Aggarwal AN, Das A. Symptomatic large bilateral adrenal metastases at presentation in small‑cell lung cancer: A case report and review of the literature. J Thorac Dis2013;5:E83‑6. 6. Madan K, Singh N. Small cell, large liver. BMJ Case Rep2012;2012. pii: bcr2012007650. 7. Morgan AH, Norris JW, Hicks JN. Palliative laser surgery for melanoma metastatic to the larynx: Report of two cases. Laryngoscope 1985;95:794‑7. 8. Koltsidopoulos P, Skoulakis C. Metastatic amelanotic melanoma of larynx‑hypopharynx. Otolaryngol Head Neck Surg 2011;144:125‑6. 9. Jagirdar J. Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung. Arch Pathol Lab Med 2008;132:384‑96. 10. Warth A, Muley T, Herpel E, Meister M, Herth FJ, Schirmacher P, et al. Large‑scale comparative analyses of immunomarkers for diagnostic subtyping of non‑small‑cell lung cancer biopsies. Histopathology 2012;61:1017‑25.
How to cite this article: Kalai U, Madan K, Jain D, Mohan A, Guleria R. Laryngeal metastasis from lung cancer. Lung India 2015;32:268-70. Source of Support: Nil, Conflict of Interest: None declared.
Lung India • Vol 32 • Issue 3 • May - Jun 2015
Copyright of Lung India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
![[Vitreous metastasis from lung cancer].](/assets/img/hold.png)
