Discussion

A variety of tumors can arise in the endobronchial tree including benign tumors, primary malignant tumors, and metastatic neoplasms. The majority of endobronchial malignant lesions are comprised of primary carcinomas of the lung and respiratory tract including adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and carcinoid tumors.

Overall, malignant melanoma (MM) consists of <2% of neoplasms of the skin; however, it remains as one of the leading causes of death related to skin cancers1. Malignant melanomas involving the lung are often a result of metastasis from a cutaneous primary2. Of patients who succumb to the disease burden of melanoma, 70% will have pulmonary involvement (multiple lung nodules or single, solitary mass) at the time of autopsy3. Primary pulmonary malignant melanoma is exceedingly rare thus all pulmonary melanomas are considered metastatic until proven otherwise2.

Cytomorphologically, melanoma can vary considerably from individual cases and within the same lesion. Malignant melanoma (MM) aspirates are often cellular due to the loss of cell cohesion and can be seen as single cells. MM can appear cytomorphologically bland with slight elevation of nuclear to cytoplasmic ratios. Often, MM can have marked pleomorphism with large, bizarre, multinucleated cells. The cells may contain intranuclear cytoplasmic invagination/inclusions and coarse nuclear chromatin. On Papanicolaou stained slides, a large eosinophilic nucleolus can be identified4. The amount of pigment can vary drastically; occasionally, a large amount of pigment can obscure the nucleus, or there can be complete absence of pigment, as seen in our case5.

Carcinoid tumor of the lung frequently occurs within the walls of the larger bronchi and is suggested to originate in the bronchial submucosal glands5. Characteristically, carcinoid tumors appear as an exophytic endobronchial lesion. Histologically, carcinoid tumors can present in multiple patterns; the tumor cells can be arranged in ribbons, trabeculae, rosettes, acini or papillary structures. Frequently in endobronchial brushings or fine needle aspirations, carcinoid tumor cells appear singly or in three dimensional clusters5. The cells are small, with uniform nuclei, stippled, granular chromatin and inconspicuous nucleoli. Typical carcinoid should lack necrosis. Atypical carcinoid tumors comprise approximately 10% of all carcinoid tumors. Atypical carcinoid tumors cytomorphologically differ from carcinoid tumors in degree of cellular pleomorphism, nuclear hyperchromasia, mitotic activity, and necrosis5.

Adenocarcinoma of the lung is the most common primary lung cancer. Primary adenocarcinomas of the lung are frequently located in the periphery of the lung, but can arise centrally4. Bronchial cytology may aid in the diagnosis depending on the size of the tumor and its location. The cytomorphology of adenocarcinoma will vary greatly depending on the predominant histological pattern6. Malignant cells can be seen singly or arranged in tightly formed, three dimensional clusters, papillary architecture with fibrovascular cores, or sheets with or without acinar formation6.

Pulmonary non-Hodgkin lymphoma is most commonly a metastasis from an extrapulmonary primary; however, it can occur as a primary lung tumor. Primary pulmonary non-Hodgkin lymphoma comprises fewer than 10% of all extranodal lymphomas4. However, 20%-50% of patients with non-Hodgkin lymphoma will develop secondary lung involvement by their respective lymphoma4.

Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) and diffuse large B-cell lymphoma (DLBCL) are the most common primary lung non-Hodgkin lymphomas4. The diagnosis of MALT lymphoma can be difficult because it resembles reactive conditions. Flow cytometric analysis is often necessary for the diagnosis of MALT lymphoma. DLBCL is cytologically easier to diagnose given the degree of cellular atypia and nuclear pleomorphism along with the aid of immunohistochemistry4.

Metastatic tumors of the lung can present as diffuse nodules or as a single tumor mass involving the major bronchus5. Occasionally, the primary site of the neoplasm can be determined by collecting clinical information in combination with cytological characteristics and architectural patterns. Adenocarcinoma is the most frequent metastatic neoplasm identified in bronchial specimens. Adenocarcinomas arising from the breast, kidney and colon are the three most common entities to metastasize to the lung. The use of immunohistochemical panels is often utilized to help determine a lung primary versus a metastatic process4,5,7.

At the time of presentation, our patient had a 6 cm mass in his right lower lobe, with satellite nodules in the same lung and multiple nodules in the left lung. Additionally he had mediastinal lymphadenopathy, endobronchial masses and multiple brain masses. Our patient was a former smoker with no prior history of melanoma or any skin cancers/lesions. The clinical picture was in favor of a metastatic carcinoma of lung primary. The presence of the endobronchial masses raised the possibility of involvement by a carcinoid tumor, although the overall clinical presentation appeared unusual for this type of neoplasms. It is critical to combine the clinical and radiologic imaging findings with the cytomorphologic findings to reach the accurate diagnosis. A broad differential diagnosis is important given the limited clinical history. Immunohistochemical work-up plays an invaluable role in identifying and confirming the correct diagnosis, as illustrated by our case.