DOI: 10.1148/rg.236035007
(Radiographics. 2003;23:1639-1643.)
© RSNA, 2003
Best Cases from the AFIP
Bronchogenic Squamous Cell Carcinoma1
Farnoosh Sokhandon, MD,
Ronald A. Sparschu, MD and
James W. Furlong, MD
1 From the Departments of Radiology (F.S., R.A.S.) and Pathology (J.W.F.), St Joseph Mercy Oakland Hospital, 44405 Woodward Ave, H-56, Pontiac, MI 48341-5023. Received January 16, 2003; revision requested February 26; revision received April 8; accepted April 8. Address correspondence to F.S. (e-mail: sokhandon@earthlink.net).
Index Terms: Bronchi, CT, 60.1211 • Bronchi, neoplasms, 60.3211 • Lymphatic system, neoplasms, 99.33
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History
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A 63-year-old man presented to the emergency department with a 1-week history of shortness of breath, which had worsened over the past 2–3 days. He also complained of a significant cough, chills, and sharp chest pains. The patient had been taking large amounts of over-the-counter nonsteroidal anti-inflammatory drugs. He had a medical history of asthma, peripheral vascular disease, hypertension, and coronary artery disease. He also had a 30-year history of smoking and had smoked 2–3 packs of cigarettes per day but had quit 2 years ago. At physical examination, scattered diffuse rhonchi and expiratory wheezing were auscultated. In addition, a few crackles that changed with deep cough were heard in the left lower lobe. The patient was admitted and underwent imaging and diagnostic studies, which established the diagnosis of stage IV lung cancer. He decided not to undergo aggressive treatment and declined any major intervention, including resuscitation. A week later, the patient became hypotensive and was found to have extensive retroperitoneal hemorrhage. However, in keeping with the patient’s wishes, no surgical intervention was performed.
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Imaging Findings
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Initial chest radiography revealed cardiomegaly and an extensive airspace area of increased opacity in the left lower lobe. Nodular prominence of the right hilum representing lymphadenopathy was also present (Fig 1). Chest radiography performed 2 years earlier had demonstrated no abnormalities. Thoracic computed tomography (CT) revealed a large (8.6 x 8.5 x 6.5-cm), lobular right hilar mass that encircled the right mainstem bronchus and the right upper and lower lobe bronchi (Fig 2a, 2b). There was an associated conglomeration of lymph nodes in the pretracheal, precarinal, and subcarinal regions and encasement of the right pulmonary artery and its branches (Fig 2c). Small, bilateral pleural effusions and airspace disease involving almost the entire left lung were also seen.
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Figure 2a. (a) Axial contrast material-enhanced chest CT scan obtained at the level of the carina shows a right hilar mass (thin arrow) and precarinal lymphadenopathy (thick arrow). (b) CT scan shows a right hilar mass that encases the right upper lobe bronchus (arrow) (cf Fig 3b, 3c). (c) CT scan demonstrates infiltration into the right lower lobe and encasement of the right lower lobe artery (arrow) (cf Fig 3b).
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Figure 2b. (a) Axial contrast material-enhanced chest CT scan obtained at the level of the carina shows a right hilar mass (thin arrow) and precarinal lymphadenopathy (thick arrow). (b) CT scan shows a right hilar mass that encases the right upper lobe bronchus (arrow) (cf Fig 3b, 3c). (c) CT scan demonstrates infiltration into the right lower lobe and encasement of the right lower lobe artery (arrow) (cf Fig 3b).
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Figure 2c. (a) Axial contrast material-enhanced chest CT scan obtained at the level of the carina shows a right hilar mass (thin arrow) and precarinal lymphadenopathy (thick arrow). (b) CT scan shows a right hilar mass that encases the right upper lobe bronchus (arrow) (cf Fig 3b, 3c). (c) CT scan demonstrates infiltration into the right lower lobe and encasement of the right lower lobe artery (arrow) (cf Fig 3b).
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Pathologic Evaluation
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An autopsy was performed, limited to examination of the thorax and abdomen. At autopsy, the right mainstem bronchus was surrounded by a tumor measuring 8.5 x 7.5 x 5.5 cm. The tumor extended into the right middle and lower lobes of the lung (Fig 3a). There was extensive hilar and mediastinal adenopathy, most of which appeared to be replaced by tumor at gross examination (Fig 3b, 3c). The tumor had a pasty, gray-white cut surface with extensive necrosis. The peripheral lung tissue showed emphysematous changes that were more apparent in the upper lobes.
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Figure 3a. (a) Photograph of the gross specimen of the lungs (coronal section) shows a right hilar mass. (b) Photograph of the gross specimen of the right lung shows a narrowed lobar artery (black arrow) between a peribronchial tumor (arrowheads) and an involved lymph node (white arrows). (c) Photograph of the gross specimen of the right mainstem bronchus demonstrates an endobronchial tumor (black arrow), pulmonary infiltration, and lobar lymph nodes with metastases (white arrows).
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Figure 3b. (a) Photograph of the gross specimen of the lungs (coronal section) shows a right hilar mass. (b) Photograph of the gross specimen of the right lung shows a narrowed lobar artery (black arrow) between a peribronchial tumor (arrowheads) and an involved lymph node (white arrows). (c) Photograph of the gross specimen of the right mainstem bronchus demonstrates an endobronchial tumor (black arrow), pulmonary infiltration, and lobar lymph nodes with metastases (white arrows).
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Figure 3c. (a) Photograph of the gross specimen of the lungs (coronal section) shows a right hilar mass. (b) Photograph of the gross specimen of the right lung shows a narrowed lobar artery (black arrow) between a peribronchial tumor (arrowheads) and an involved lymph node (white arrows). (c) Photograph of the gross specimen of the right mainstem bronchus demonstrates an endobronchial tumor (black arrow), pulmonary infiltration, and lobar lymph nodes with metastases (white arrows).
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Microscopic examination showed that the tumor arose from the right mainstem bronchus, with extensive patchy geographic areas of necrosis rimmed by nested arrangements of viable cells. These cells were large epithelial cells and featured enlarged nuclei with malignant cytologic features. The cytoplasmic borders in many areas were indistinct, but in other areas intercellular bridging was apparent, a finding consistent with a squamous origin. A few small sheetlike areas of pavemented squamous cells were also noted (Fig 4), but no extracellular keratin pearls were found. No glandular or neuroendocrine features were seen. The tumor was histologically classified as a poorly differentiated squamous cell carcinoma. The hilar and mediastinal lymph nodes were extensively replaced by metastatic carcinoma. The liver, kidneys, adrenal glands, and vertebral bone marrow were free of metastatic carcinoma.
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Figure 4. Photomicrograph (original magnification, x400; hematoxylin-eosin stain) of a right middle lobe tumor reveals polygonal epithelial cells with occasional intercellular bridges (arrow), findings that indicate squamous differentiation.
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Discussion
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Bronchogenic carcinoma, a malignant neoplasm with an alveolar or bronchial origin in over 99.5% of cases (1), is the most common cancer and cause of cancer-related death in both men and women (2). It is divided into four main histologic subtypes on the basis of gross and microscopic features: adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and large cell carcinoma.
Squamous cell carcinoma is the second most common subtype of bronchogenic carcinoma (approximately 30%–40% of all cases) (3). The most common subtype is adenocarcinoma. When cell types are analyzed by gender, men have a relative increased frequency of adenocarcinoma and women have a relative increased frequency of squamous cell and small cell carcinoma. However, there is an absolute increase in the frequency of adenocarcinoma despite its decreased frequency relative to squamous cell and small cell carcinoma in women.
Exposure to toxic agents (eg, nickel) increases the risk of developing squamous cell carcinoma (3). There is an increased risk for developing lung cancer that is proportional to the number of cigarettes smoked per day. Interestingly, this dose response for squamous cell carcinoma is weak among men and strong among women (4). Squamous cell carcinoma is most often associated with familial clustering of cancer, particularly among women; persons under 57 years old; and individuals who smoked for fewer than 20 years (5).
At histologic analysis, squamous cell carcinoma is characterized by invasion of the bronchial wall by nests of malignant cells with abundant cytoplasm. The formation of keratin pearls and intercellular bridges, seen in well-differentiated tumors, is specific for this tumor (the tumor histologically mimics differentiation of the epidermis by producing keratin "epidermoid carcinoma"). Tumors with squamous histologic features can sometimes elicit a sarcoid reaction in nodes, resulting in nodal enlargement without metastatic spread (3). In most cases of squamous cell carcinoma, the tumor arises centrally within a lobar or segmental bronchus. In a Marshfield Clinics study (1), 43% of squamous cell carcinomas manifested with a peripheral origin and 61% manifested with a central mass, representing both central primary sites and lymph node metastasis. At gross examination, these tumors are polypoid masses that grow into the bronchial lumen while simultaneously invading the bronchial wall. Squamous cell carcinomas are the least likely of all bronchogenic carcinomas to distantly metastasize (<20% of cases at presentation) (3). The mode of spread is direct extension to the local lymph nodes. These tumors demonstrate the slowest growth rate of all bronchogenic carcinomas. The central location and endobronchial component of the tumor account for the presenting symptoms of cough and hemoptysis and the common radiographic finding of a hilar mass with or without obstructive pneumonitis or atelectasis (2). Evidence of bronchial obstruction is seen in 56% of affected patients (6). Central necrosis is common in large tumors. Central cavitation is common if there is communication between the central portion of the mass and the bronchial lumen. Of all bronchogenic carcinomas, squamous cell carcinoma is the most likely to cavitate (about 15% of cases) (6).
Squamous cell carcinoma is the most common tissue type among the different types of bronchogenic carcinoma that manifest as a Pancoast tumor (superior sulcus tumor), a rare form of bronchogenic carcinoma (1% of cases) that arises in the superior sulcus of the lung apex. Adenocarcinoma may also occur at this site. These tumors often lead to invasion of the pleura and rib, producing shoulder pain that is often treated as musculoskeletal pain. Involvement of the lower roots of the brachial plexus cause arm pain and paresthesias in the ulnar nerve distribution. The tumor may spread to the sympathetic ganglion, leading to Horner syndrome, which manifests as ipsilateral enophthalmos, miosis, partial ptosis, and anhidrosis. Squamous cell carcinomas are commonly associated with clubbing and hypertrophic osteoarthropathy. Hypercalcemia is also commonly observed secondary to a parathyroid hormone–like peptide created by the tumor (3).
Chest radiography is readily available and inexpensive and is useful in the work-up of lung cancer patients. Therefore, it is the most frequently used modality for initial investigation. Unfortunately, squamous cell carcinoma is the most common radiologically occult bronchogenic carcinoma: The overlapping soft-tissue areas of increased opacity may hide small endobronchial lesions. As stated earlier, squamous cell carcinoma commonly manifests as a central or hilar mass. This mass may have an irregular or indistinct margin due to tumor infiltration, an irregular desmoplastic response to tumor growth, or an irregular contraction in the central portion of the tumor. Conversely, solid tumor growth may be associated with a well-defined tumor margin with or without displacement of adjacent structures (7). CT is valuable in diagnosing early-stage squamous cell carcinoma, particularly when lesions show polypoid growth or invade the cartilaginous layer. In a study by Saida et al (8), over one-half of early-stage squamous cell carcinoma lesions that showed polypoid growth or reached the cartilaginous layer of the bronchial wall could be seen at CT with 5.0-, 3.0-, or 1.5-mm sections. Contrast-enhanced CT may help distinguish malignant from benign lesions. At contrast-enhanced CT, malignant lesions enhance more than benign lesions; however, active granulomas or other infectious lesions can also enhance (9). Magnetic resonance (MR) imaging is superior to CT in evaluating local invasion and detecting hilar lymphadenopathy. It is particularly useful in evaluating superior sulcus tumors. Invasion of the brachial plexus, subclavian vessels, and adjacent vertebral bodies can also be depicted at MR imaging. MR imaging may be slightly more accurate than other techniques in detecting extranodal tumor extension into the mediastinum. Positron emission tomography (PET) has a higher sensitivity, specificity, and accuracy than CT in staging mediastinal disease (3). Sensitivity for detecting lung cancer increases from 66% with CT alone to 95% with CT and PET combined. PET can aid in diagnosis, staging, assessing recurrence, and monitoring response to therapy.
Accurate clinical staging is crucial to proper selection of surgical patients. Confirmatory diagnostic nodal biopsy with mediastinoscopy, anterior mediastinotomy, or transbronchial needle biopsy in patients with nodes whose short-axis diameter exceeds 1 cm at CT or with nodes that are positive at PET is very important in preoperative determination of nodal status (10). Endoscopic ultrasonography alone or with fine-needle aspiration biopsy adds useful diagnostic information in determining metastasis to posterior mediastinal or subcarinal lymph nodes in patients with non–small cell lung cancer. These procedures are especially helpful in the preoperative evaluation of patients with suspicious contralateral mediastinal or "bulky" subcarinal nodes (11).
Although some early-stage squamous cell carcinomas are incurable, Miura et al (12) showed that lack of pericartilage invasion and a staging of T1 N0 M0 or lower are characteristic of better survival rates. The prevalence of multiple primary bronchogenic cancers, especially squamous cell carcinoma, has been increasing owing to improved early detection and cancer therapy. Multiple endobronchial squamous cell carcinomas may be difficult to resect due to poor pulmonary function. Induction chemotherapy is another treatment option in affected patients (13).
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Footnotes
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Abbreviations: PET = positron emission tomography
Editor’s Note. —Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. With each issue of RadioGraphics, one or more of these cases is published with each issue of the Journal, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
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References
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- Quinn D, Gianlupi A, Broste S. The changing radiographic presentation of bronchogenic carcinoma with reference to cell types. Chest 1996; 110:1474-1479.[Abstract/Free Full Text]
- Rosado-de-Christenson ML, Templeton PA, Moran CA. Bronchogenic carcinoma: radiologic-pathologic correlation. RadioGraphics 1994; 14:429-448.[Abstract]
- Sharma S, Maycher B, Tsuyuki S. Lung cancer, non–small cell. Available at: www.emedicine.com/radio/topic406.htm. Accessed January 2003.
- Morabia A, Wynder EL. Cigarette smoking and lung cancer cell types. Cancer 1991; 68:2074-2078.[CrossRef][Medline]
- Ambrosone CB, Rao U, Michalek AM, Cummings KM, Mettlin CJ. Lung cancer histologic types and family history of cancer: analysis of histologic subtypes of 872 patients with primary lung cancer. Cancer 1993; 72:1192-1198.[CrossRef][Medline]
- Jain NK, Madan A, Sharma TN, Agnihotri SP, Saxena A, Mandhana RG. Bronchogenic carcinoma: a study of 109 cases. J Assoc Physicians India 1989; 37:379-382.[Medline]
- Sone S, Sakai F, Takashima S, et al. Factors affecting the radiologic appearance of peripheral bronchogenic carcinomas. J Thorac Imaging 1997; 12:159-172.[Medline]
- Saida Y, Kujiraoka Y, Akaogi E, Ogata T, Kurosaki Y, Itai Y. Early squamous cell carcinoma of the lung: CT and pathologic correlation. Radiology 1996; 201:61-65.[Abstract/Free Full Text]
- Swensen SJ, Brown LR, Colby TV, Weaver AL, Midthun DE. Lung nodule enhancement at CT: prospective findings. Radiology 1996; 201:447-455.[Abstract/Free Full Text]
- British Thoracic Society; Society of Cardiothoracic Surgeons of Great Britain and Ireland Working Party. BTS guidelines: guidelines on the selection of patients with lung cancer for surgery. Thorax 2001; 56:89-108.[Free Full Text]
- Gress FG, Savides TJ, Sandler A, et al. Endoscopic ultrasonography, fine-needle aspiration biopsy guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small-cell lung cancer: a comparison study. Ann Intern Med 1997; 127:604-612.[Abstract/Free Full Text]
- Miura H, Nakamura H, Taira O, Uchida O, Kato H, Konaka C. Outcome of patients with early stage lung cancer. Surg Today 1998; 28:736-739.[CrossRef][Medline]
- Kameyama K, Huang CL, Hayashi E, et al. Induction chemotherapy before operation for multiple endobronchial squamous cell carcinoma of the lung. Ann Thorac Surg 2002; 74:1008-1010.[Abstract/Free Full Text]
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History
Imaging Findings
