July 2014

A 66 year-old man with recurrent bronchopneumonia

Derrick Green, MD, Patrick Bacaj, MD, and Vernard Adams, MD

Overview

The patient was a 66 year old man with a history of pulmonary emphysema and recurrent bronchopneumonia, who required home oxygen therapy. He had poorly-controlled type II diabetes mellitus, a neurogenic bladder, and an indwelling urinary catheter. He had essential hypertension, and an abdominal aortic aneurysm had been repaired with an endovascular stent in the past. He reported a history of both military and civilian exposure to Agent Orange and asbestos.

He presented with shortness of breath. A computed tomography scan showed bilateral pleural effusions and dense opacification in the peripheral and posterior aspects of the lungs suspicious for pneumonia, as well as mediastinal lymphadenopathy. An autoimmune workup including anti-ds DNA, anti-nuclear, anti-Smith, anti-RO, anti-LA, p-ANCA, and c-ANCA panels was negative. A bone marrow biopsy revealed no myelodysplasia, acute leukemia, or marrow infiltrative process. A thoracoscopy was performed during which parietal pleural biopsies and a right middle lobe wedge resection were taken and submitted for pathologic evaluation. The patient remained intubated and sedated after surgery. He developed arterial hypotension requiring intravenous fluids and vasopressors.  After discussion with the family, do not resuscitate and comfort care orders were placed. He expired shortly after being extubated.

Gross Description

At autopsy the pleural cavities were obliterated by thick, gray-pink, fibrous adhesions. The right lung weighed 1,030 grams and the left weighed 610 grams. The lungs had numerous, large, consolidated areas with firm, gray-green, and pale cut surfaces. The consolidated areas expressed yellow purulent material with pressure. Areas of firm black discoloration were between the lungs and the fibrous adhesions. An isolated focus of caseous necrosis was in the right lower lobe. The lung parenchyma uninvolved by the areas of consolidation was congested and edematous.

Figure 1. The right lung had a focus of pale yellow consolidation at the visceral pleura. The surrounding lung parenchyma had fibrosis.
Figure 2. Parallel slices of the right lung with numerous foci of gray-green and pale yellow consolidation.
Figure 3. Cytology preparation from a brochoalveolar lavage showing a three-dimensional cluster of cells with large nuclei and indistinct cell borders, suspicious for adenocarcinoma
Figure 4. Specimen from wedge resection of the right middle lung lobe. Malignant appearing glands producing mucin are within a fibrotic stroma.
Figure 5. Surgical specimen. The tumor cells are strongly positive for CK7.
Figure 6. The tumor cells are strongly positive for CK20.
Figure 7. The tumor cells are negative for TTF-1.
Figure 8. Lung section from autopsy. The tumor has abundant mucin production.
Figure 9. Lung section from autopsy. Crowded columnar, mucin-secreting cells line alveolar air spaces.
Figure 10 and Figure 11. Photomicrographs at low and high power of lung sections from autopsy specimen. The cells are brightly eosinophilic and have squamous differentiation with several foci of keratinization.

Diagnosis

The squamous component comprised less than 5% of the tumor mass, and the cells stained negative for calretinin. What is the most likely diagnosis?

Answer

Please select an answer above.

Discussion

Adenocarcinoma, the most common type of lung cancer, accounts for about 40% of all invasive lung cancer in the United States. The incidence has been increasing in the past decade. It is the most common variant seen in women and non-smokers. Interestingly, its association with smoking is weaker than with other types of lung carcinoma.[1]

The disease usually arises as a single mass or as multiple nodular tumors of variable size. The tumors are gray-tan, firm, and have variable amounts of necrosis. The tumors may be endobronchial or peripheral, where they can cause retraction at the periphery leading to a puckered appearance of the pleura. They can also be associated with a pneumonia-like consolidation, and this presentation is typically associated with bronchioloalveolar, as in this case, or papillary microscopic patterns. Other grossly appreciable patterns include pleural-based adenocarcinoma arising in a background of fibrosis, and diffuse bilateral lung disease.[2]

Microscopically, adenocarcinoma of the lung has patterns that vary by degrees of differentiation and atypia. Recently the term “bronchioloalveolar carcinoma” was dropped from the classification system and two new entities were recently added to include minimally invasive adenocarcinoma and adenocarcinoma in situ. Minimally invasive adenocarcinomas are defined as small solitary adenocarcinomas with predominantly lepidic growth and <= 5 mm invasion, while adenocarcinoma in situ is defined as small solitary adenocarcinomas with pure lepidic growth. Lepidic refers to the tendency of the tumor to grow in a creeping fashion along the alveolar walls. [3]

Invasive adenocarcinomas are classified by the predominant growth pattern to include lepidic, acinar, papillary, solid, and micropapillary. Variants include mucinous, colloid, fetal, and enteric features. In this case the tumor displayed a lepidic growth pattern and produced abundant mucin, so “adenocarcinoma with mucinous features” was the diagnosis given. Pleural invasion was noted. The staining pattern in this tumor was a bit unusual in that it stained positive for both CK7 and CK20, while staining negative for TTF-1. However, males and smokers are more likely to have TTF-1 negative tumors. Furthermore, in one case series, 17 of 19 cases of mucinous adenocarcinoma stained either moderately or strongly positive for CK20.4 These staining patterns illustrate the caveat that immunohistochemical stains must be interpreted within the context of each individual case.

Adenosquamous carcinoma is the term used to describe tumors in which squamous and glandular differentiation are found in the same neoplasm in roughly the same amount. In this case there was only a small focus of squamous differentiation in the left upper lung lobe comprising less than 5% of the total tumor volume. Therefore, the tumor did not meet the criteria for adenosquamous carcinoma. Keratin formation was identified, so the squamous component was classified as being moderately differentiated. The squamous component identified represented divergent differentiation of the antecedent adenocarcinoma.

References

  • Gattuso P, Reddy VB, Odile D, Spitz D, and Haber M. Differential Diagnosis in Surgical Pathology, 2nd ed. Philadelphia: Saunders; 2010. p.258-280.
  • Rosai J. Rosai and Ackerman's Surgical Pathology, 10th ed. Edinburgh: Mosby Elsevier; 2011. p. 340-401.
  • Yankelewitz D, Henderson D, Wistuba I, et.al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thorac Oncol. 2011 6(2):244-285.
  • Shah RN, Badve S, Papreddy K, et al. Expression of cytokeratin 20 in mucinous bronchioloalveolar carcinoma. Human Pathology. 2002 333(2):915-20.