Non-Small Cell Lung Cancer Presenting as Anterior Nasal Mass and Epistaxis

Abstract

Lung malignancy presentation with an uncommon metastatic site is a diagnostic challenge and often associated with poor prognosis. Nasal cavity is a rare metastatic site for any type of lung cancer. We report an unusual case of poorly differentiated adenosquamous carcinoma of the lung with widespread metastasis presenting as a right vestibular nasal mass with epistaxis. A 76-year-old male patient with chronic obstructive pulmonary disease and 80 pack-year smoking history presented with spontaneous epistaxis. He reported a new rapidly growing right-sided nasal vestibular mass first noticed 2 weeks prior. Physical examination showed fleshy mass with crusting in right nasal vestibule along with a left nasal domus mass. Imaging revealed an ovoid mass in the right anterior nostril and a large mass in the right upper lobe of the lung (RULL) along with thoracic vertebral sclerotic metastasis and large left frontal lobe hemorrhagic lesion with severe vasogenic edema. Positron emission tomography scan showed large right upper lobe mass and suspected to be the primary malignancy along with widespread metastasis. Biopsy of the nasal lesion revealed poorly differentiated non-small cell carcinoma with squamous and glandular features. The diagnosis of very poorly differentiated adenosquamous carcinoma of the lung with widespread metastasis was made. In conclusion, unusual metastatic sites with unknown primary lesions require a thorough diagnostic workup involving biopsy and extensive imaging. Lung cancer with unusual metastatic sites is inherently aggressive and associated with poor prognosis. Multidisciplinary treatment modalities should be employed keeping in view the functional status and comorbidities of the patient.

Introduction

Lung cancer can present in multiple ways involving signs and symptoms secondary to local invasion, metastatic spread, or systemic manifestations of malignancy. Common sites of metastases include brain, bone, liver, adrenal glands, and lymph nodes.¹ Cases with unusual metastatic sites have been reported and pose diagnostic challenges as well as heralding an advanced stage malignancy with poor prognosis. The poor prognosis can be secondary to the advanced stage of the malignancy at the time of diagnosis with uncommon metastatic site, or the inherent aggressive and invasive nature of the primary lesion. It is extremely uncommon for a nasal vestibular mass to be the primary manifestation of a lung malignancy. We report such a case of a rapidly growing nasal mass causing epistaxis as the initial clinical manifestation of poorly differentiated non-small cell adenosquamous carcinoma of the lung.

Case Presentation

A 76-year-old male patient presented to the emergency department with epistaxis. He reported a right vestibular nasal mass which had grown rapidly more than the past 1 to 2 weeks along with spontaneous epistaxis. Upon further history, he reported intermittent coughing and dysphagia, right otalgia, tinnitus, and intermittent frontal headaches for the past 2 months. He denied any prior nasal lesions, weight loss, change in appetite, disequilibrium, odynophagia, or change in voice quality. The patient and his wife reported preserved executive function with no recent change in personality. He had an 80 pack-year cigarette smoking history and had quit date 2 years prior to this episode. Medical comorbidities included severe chronic obstructive pulmonary disease, chronic kidney disease stage IV, and a prior stroke.

Physical examination showed a large right nasal vestibular lesion, measuring approximately 4 cm with a fleshy appearance and overlying crusting. It occupied almost the entire nasal vestibule with no obvious extensions to adjacent anatomical sites. In addition, there was a 1.5 cm exophytic mass on the left nasal domus (Figure 1A-C). No cervical lymphadenopathy or any other significant findings were identified. Flexible fiberoptic examination confirmed a nasal vestibular lesion confined to the right nasal cavity with an unremarkable nasopharynx, oropharynx, larynx, and hypopharynx, and a biopsy was performed. Computerized tomographic (CT) scanning revealed an ovoid mass in the right anterior nostril. In addition, there was a 5.5 cm × 5.2 cm × 3.8 cm mass in the RULL along with a 3.2 cm × 3 cm × 2.3 cm spiculated mass in the right infrahilar region, and a 2.6 cm × 2.1 cm right thyroid lesion and sclerotic lesions in the thoracic vertebrae (Figure 2A-C). Magnetic resonance imaging (MRI) of the brain showed a 4.6 cm × 3.2 cm × 3.6 cm left frontal lobe hemorrhagic mass with vasogenic edema resulting in midline shift and subfalcine herniation along with parietal lesions (Figure 2D). Positron emission tomography (PET) scan showed a hypermetabolic anterior nasal mass with standardized uptake values (SUV) of 15.6. There was a right upper lobe mass measuring up to 6.5 cm with SUV of 15.3, favored to reflect the site of primary malignancy, in addition to hypermetabolic lesions in the right hilum, thyroid, brain, prostate, and right proximal femur (Figure 3A-C).

Figure 1.

Right nasal vestibular mass with an exophytic mass on the left nasal domus. (A) Oblique view, (B) frontal view, and (C) lateral view.

Figure 2.

(A) Computerized tomographic (CT) scan of head and neck showing an ovoid mass in the right anterior nostril. (B) CT scan of head and neck showing exophytic mass originating from the right thyroid lobe. (C) CT scan of chest showing large mass in the RULL along with a spiculated mass in the right infrahilar region. (D) Magnetic resonance imaging of the brain showed a large left frontal lobe hemorrhagic mass with severe vasogenic edema resulting in midline shift.

Abbreviation: RULL, right upper lobe of the lung; CT, computerized tomographic.

Figure 3.

(A) Positron emission tomography scan with a right upper lobe mass with SUV of 15.3, reflecting site of suspected primary malignancy. (B) Whole-body PET scan with hypermetabolic lesions in lungs, hilum, vertebrae, pelvis, and right shoulder. (C) Hypermetabolic nasal lesion.

Abbreviations: SUV, standardized uptake values; PET, Positron emission tomography.

Histopathology of right nasal vestibule biopsy revealed poorly differentiated non-small cell carcinoma with squamous and glandular features (Figure 4A and B). The stains were positive for positive for epithelial membrane antigen (EMA), anti-human epithelial antigen (Ber-EP40), thyroid transcription factor-1 (TTF-1), and cytokeratin 7 (CK7), which are markers for adenomatous differentiation (Figure 4C and D), while also being positive for cytokeratin 5/6 (CK5/6) and p40 marker for squamous differentiation (Figure 4E and F). Neural-cell adhesion molecule (NCAM/CD 56) stain was negative for evidence of neuroendocrine differentiation. Thyroid transcription factor-1 positivity was suggestive of metastasis from a primary lung lesion as morphology was not consistent with either thyroid or prostate primary. Further testing for mutations was negative for v-raf murine sarcoma viral oncogene homolog B1 (BRAF), endothelial growth factor receptor (EGFR), ROS1, and anaplastic lymphoma kinase (ALK) rearrangement with low expression (1%) of programmed death-ligand 1 (PDL1). Considering the extensive metastasis, multiple brain lesions, no immunotherapy options, and poor performance status with an Eastern Cooperative Oncology Group (ECOG) of 3, a decision of neoadjuvant radiotherapy was made. However, his condition continued to deteriorate and eventually passed away.

Figure 4.

(A) H&E (hematoxylin and eosin) sections show multiple infiltrating squamoid nest of poorly differentiated malignant cells with comedo necrosis. (B) The pleomorphic malignant cells are medium-to-large size with prominent nucleoli. Frequent mitotic figures and apoptotic cells are also present. (C and D) Both TTF-1 and CK7 highlight malignant cells, which favor adenocarcinoma. (E and F) CK5/6 and p40 highlight malignant cells and favor squamous cell carcinoma.

Abbreviations: TTF-1, thyroid transcription factor-1; CK7, cytokeratin 7; CK5/6, cytokeratin 5/6; ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1.

Discussion

The nasal cavity is an unusual site of metastasis originating from primary lung cancer. While the involvement of paranasal sinuses by metastasizing lung cancer has been well reported in the literature, the development of isolated nasal cavity lesions remains a rare phenomenon.² Other uncommon anatomical sites that may be involved by lung cancer include soft tissue, kidneys, pancreas, spleen, peritoneum, intestine, bone marrow, eye, ovary, thyroid, heart, breast, and tonsil.¹ However, the bizarre presentation and the rapid enlargement of the nasal mass more than a 2-week period in our patient were quite unusual for metastasizing lung cancer. Haymes et al reported a similar presentation for small-cell lung cancer with a more chronic clinical course. The patient had a 4-month history of unilateral rhinorrhea, maxillary hypoesthesia, hyposmia, and hypogeusia. On further workup, he was subsequently diagnosed with small-cell carcinoma of the lung.³ Similarly, squamous cell carcinoma of the lung has also been reported to present as a nasal-tip mass growing more than a 3-month interval.⁴ Huang et al have reported metastatic spread to paranasal sinus along with a literature review of similar cases. Interestingly, paranasal metastatic lesions were found to be more commonly associated with adenocarcinoma of the lung.⁵ However, given the rarity of nasal and paranasal metastasis, it is difficult to ascertain whether a particular type of lung malignancy has an increased propensity to spread to the nasal cavity.

Apart from lung cancer, a few other malignancies have been reported to involve nasal and paranasal cavities. Again, paranasal sinuses appear to be more commonly affected than the nasal cavity. In a retrospective literature review conducted by Prescher et al, there were a total of 169 reported cases of metastases to paranasal sinuses with renal cancer as the most common primary malignancy and maxillary sinus as the most commonly involved sinus.² A presentation similar to our case was reported by Georgy et al in a patient with renal cell carcinoma presenting as a nasal cutaneous horn along with multiple gingival and scalp nodules.⁶ In addition, Yoo et al reported hepatocellular cancer metastasis to the right nasal cavity with massive epistaxis.⁷ Likewise, other cases were notable for breast cancer metastasis to zygomatic bone and maxillary sinus, uterine cervix cancer to nasal dorsum, and prostate cancer to the frontal sinus.^2,8,9

The differential diagnosis of nasal masses differs widely according to the age of the patient. They may be congenital, inflammatory, neoplastic (primary or metastatic), or traumatic in nature. Although masses in the anterior nasal cavity or involving the nasal ala can be readily apparent at clinical examination, those in the posterior nasal cavity and nasopharynx are often difficult to visualize on physical examination. In addition, the signs and symptoms of these lesions tend to be nonspecific and may mimic signs of upper respiratory tract symptoms causing a further delay in diagnosis. Therefore, a detailed history and a focused physical examination are of utmost importance which should include nasoendoscopy in suspected cases. If the sinonasal mass is the first presenting complaint without the diagnosis of a previously known malignancy, the diagnostic workup needs to be thorough. Especially in instances where the nasal or paranasal masses are accompanied by worsening headache and evolving visual symptoms, the probability of an aggressively invading malignant lesion becomes likely.⁵ Whenever suspected, a low threshold for tissue biopsy of the nasal lesion and whole-body imaging is required to establish the diagnosis.

Poorly differentiated lung cancer lesions are aggressively growing tumors and usually metastatic at the time of the diagnosis. Reportedly, as many as half the lung cancer cases are metastatic at the time of diagnosis and metastases involving unusual sites typically render a poor prognosis.¹ If there are multiple lesions with unknown primary, the diagnosis becomes challenging. Detailed imaging and biopsy specimens are needed to ascertain the occult primary. A combination of local and systemic therapy has been shown to improve survival rates compared with systemic therapy alone.¹ This demands that patients such as ours are offered local excision or radiation in addition to systemic chemotherapy to offer them an improved chance at survival.