Keywords
adenocarcinoma of lung - multiple primary - vocal cord palsy
Introduction
Double primary malignancy is not uncommon.[1]
[2]
[3]
[4] In 1934, Bugher was the first to analyze double primary malignancy statistically.[5] The prevalence of multiple primary malignancies ranges from 0.7 to 11.7%.[6] Most diagnosed double primary were metachronous in comparison to synchronous.[7] The increased incidence of double primary is probably due to possible genetic susceptibility
and exposure to environmental carcinogens.[8] The mean age for reporting second primary cancer is around 50 years or above.[9]
[10]
[11] Patients with digestive, urogenital, and respiratory tumors are likely to develop
multiple primary metachronous tumours.[12] Metastasis of basal cell carcinoma is rare, ranging between 0.0028 and 0.55%.[13] Here, we present a rare case of basal cell carcinoma of the skin along with adenocarcinoma
of the lung with bilateral vocal cord palsies.
Case Report
A 44-year-old man, known diabetic, presented with hoarseness of voice for 3 months.
He gave a history of pulmonary tuberculosis and completed antitubercular treatment
2 years ago. On examination, we noted a single, nontender, blackish growth measuring
about 2 × 1 cm on the left side of the nose, adjacent to the medial canthus of the
left eye ([Fig. 1A]). The patient noticed it but did not seek medical help considering it a normal mole.
On indirect laryngoscopy and video laryngoscopy, the bilateral vocal cords were in
the paramedian position ([Fig. 1B]). Contrast-enhanced computed tomography showed mild enhancing wall thickening of
the esophagus, with enhancing nodular lesion of the right lobe of the lung and heterogeneously
enhancing lesion of the right lobe of the liver ([Fig. 2A]). Multiple enlarged lymph nodes were noted in the pretracheal, paratracheal, tracheobronchial,
and right supraclavicular area, with multiple nodules in both thyroid lobes ([Fig. 2B]). Flexible gastroesophageal endoscopy was normal. Bronchoalveolar lavage was suggestive
of malignant nonsmall cell lung carcinoma. Biopsy from the lateral basal segment of
the right lower lobe bronchus mass suggested moderately differentiated adenocarcinoma
([Fig. 3A]). The molecular study was positive for ALK (D5F3) and negative for ROS1 (D4D6) ([Fig. 3B]). Magnetic resonance imaging metastasis workup showed marrow signal changes involving
multiple vertebrae, pelvic bones, and neck of the left femur, showing diffusion restriction
suggestive of metastasis, without any intracranial metastasis. The biopsy from the
nasal lesion was suggestive of basal cell carcinoma ([Fig. 4]). Fine-needle aspiration cytology of the pretracheal lymph node was suggestive of
metastatic adenocarcinoma, whereas in thyroid it was suggestive of colloid nodular
goiter. Considering the metastatic spread of the adenocarcinoma, the patient was started
on chemotherapy meanwhile kept under close observation for the progression of basal
cell carcinoma and development of respiratory stridor. The patient underwent six cycles
of chemotherapy (pemetrexed/carboplatin × 6 cycles + GCSF × 4 cycles and crizotinib).
Positron emission tomography after six cycles of chemotherapy was suggestive of a
partial response to chemotherapy. The basal cell carcinoma of the nose responded to
the chemotherapy with significant reduction in its size. Currently, the patient is
on crizotinib maintenance therapy on a compassionate basis due to his poor socioeconomic
status until a complete response will be obtained. The patient refused to undergo
surgical excision of basal cell carcinoma as there was a significant reduction in
the size of the tumor and he wants to get it done later. At present, there is no stridor
and the patient is kept on close observation.
Fig. 1 (A) Blackish growth on the left side of the nose, adjacent to the medial canthus of
the left eye. (B) Vocal cords in paramedian position.
Fig. 2 (A) Contrast-enhanced computed tomography (CECT) neck with thorax showing enlarged nodular
lesion of right lower lobe. (B) CECT neck, red arrow showing enlarged right paratracheal lymph node, yellow arrow
showing nodule in the right lobe of thyroid.
Fig. 3 (A) Microscopic picture of adenocarcinoma showing tumor cells arranged in acinar formation
with high nuclear-to-cytoplasmic ratio (10× magnification). (B) Immunohistochemistry suggestive of positive ALK (D5F3) marker (10× magnification).
Fig. 4 Microscopic picture of basal cell carcinoma showing basaloid cells seen in island
arrangements, peripheral palisading pattern noted (10× magnification).
Discussion
Multiple primary cancers are classified as synchronous and metachronous. Those malignancies
observed at the same time or within 6 months are termed synchronous, and those cancers
that develop at more than a 6-month interval are termed metachronous.[14] Synchronous multiple primary cancers were first reported by Beyreuther.[15] Second primary cancers have been increasing in recent years. This is probably due
to an increased survival rate and improved imaging technology.
Basal cell carcinoma is the most common low-grade skin carcinoma. The usual site for
basal cell carcinoma is exposed head and neck areas. Metastatic basal cell carcinoma
is rare. Metastasis usually occurs in regional lymph nodes, lungs, and bones.[16] The primary treatment is surgical excision. In metastatic cases of basal cell carcinoma,
wide surgical excision along with chemoradiation is the treatment modality.[13]
Lung adenocarcinoma is a fatal disease, despite significant progression in management,
such as surgical resection, ablation, and targeted therapy.[16] In the recent 5 years, the survival rate of lung cancer has been 22%.[17] Ventana anti-ALK (D5F3) CDX assay is an Food and Drug Administration-approved method
for the qualitative detection of ALK (anaplastic lymphoma kinase protein) in formalin-fixed
paraffin-embedded nonsmall cell lung carcinoma tissue stained with Benchmark XT, or
Benchmark Ultra automated staining instrument. The presence of strong granular cytoplasmic
staining in tumor cells (any percentage of tumor cells) is considered as positive.[18]
[19] It helps identify patients who may benefit from crizotinib, ceritinib, and alectinib
treatment.
Bilateral abductor palsy was probably due to the involvement of pretracheal, paratracheal,
and mediastinal lymph nodes in this case. The malignant infiltration of the upper
lobe of the lung can be the cause for recurrent laryngeal nerve palsy. But lung malignancies
mainly involve the left recurrent laryngeal nerve. Other differential diagnoses are
malignant conditions of the thyroid. Our patient had benign thyroid nodules, unlikely
to cause bilateral recurrent laryngeal nerve palsy. Fibrotic changes following tuberculosis
could also be a possible differential diagnosis in our patient, as this patient had
tuberculosis in the past. Preexisting undiagnosed unilateral vocal cord palsy could
be one of the causes. The patient could now be symptomatic due to the involvement
of the other recurrent laryngeal nerve. Early evaluation and management may prevent
the extensive spread in this case. Our patient was not on stridor, so he was kept
on observation and close follow-up.
In the case of dual malignancy, the priority is for the management of advanced malignancy.
Both can be dealt with simultaneously if amenable to surgical resection.[20] The multidisciplinary team approach is required in multiple primaries. The proper
counseling of the patient regarding the therapeutic challenges and uncertainty about
the prognosis is a must.
Systemic chemotherapy is preferred if both tumors are likely to respond to the same
chemotherapeutic drugs, for example, squamous cell carcinoma of the head and neck
and squamous noncell carcinoma of the lungs.[21] Though chemotherapy does not play a significant role in basal cell carcinoma, surprisingly,
in this case response was good. Unfortunately, dual malignancies are less understood.
This probably is due to most of the clinical trials exclude multiple primaries.
In this case, the management of lung adenocarcinoma was prioritized due to its metastatic
spread and aggressive nature. Subsequently, the basal cell carcinoma and vocal cord
palsy will be managed depending on the patient's response to chemotherapy. Counseling
the patient and providing adequate information regarding their condition plays a crucial
role in managing multiple primary malignancies.
Conclusion
Malignancy is the most common extralaryngeal cause of vocal cord palsy. Surgical resection
is the best modality of management for basal cell carcinoma unless it is in the advanced
stage. Chemoradiation would be the ideal modality of management in dual malignancies.
In conclusion, a thorough evaluation is a must while evaluating any malignancy to
rule out the presence of a second primary.
