Contributed by Jay S Raval, MD and Larry Nichols, MD
This 77-year-old white male had insulin-dependent diabetes mellitus, hyperlipidemia, peripheral vascular disease, hypothyroidism, peptic ulcer disease attributed to non-steroidal anti-inflammatory drug use, and a remote smoking history.
Starting three years previously, the patient began to notice a significant decline in his exercise tolerance as well as worsening dyspnea. His shortness of breath was not significantly relieved by respiratory nebulizer therapy. He was placed on supplemental oxygen therapy. Recurrent left pleural effusions prompted talc pleurodesis one year prior. Cytology of the fluid at an outside hospital revealed no malignancy. He had chronic pleuritic chest pain and a computed tomography scan two months later revealed bilateral, moderately advanced pulmonary fibrosis, mild traction bronchiectasis, scattered ground glass opacities and left apex opacity. The fibrosis had a subpleural distribution with honeycombing pattern consistent with usual interstitial pneumonia. Pulmonary function testing that day showed a forced vital capacity of 1.5 liters, 33% of predicted, and forced expiratory volume in 1 second of 1.1 liters, 83% of predicted, indicative of restrictive lung disease. Biopsy of solid areas in the lungs at an outside hospital revealed no malignancy.
Over the next 7 months, the patient's dyspnea worsened, primarily in a slowly progressive fashion, but acutely at times. Cardiac catheterization revealed up to 70% stenosis of an obtuse marginal coronary artery, a mean pulmonary artery pressure of 15 mmHg (24/7 mmHg) and mean wedge pressure of 4 mmHg. His oxygen requirement increased to 3 liters/minute at rest and 7 liters/minute with exertion. He developed a partially compensated respiratory acidosis with arterial pH 7.33, pCO2 73 mmHg and bicarbonate 38 mEq/L. Computed tomography showed only mild interval changes in his lung disease. A comprehensive autoantibody screen was negative (ANA <40, ANCA <20, rheumatoid factor <20, RNP antibody negative, Sm antibody negative, Jo-1 negative, and normal C3 and C4). The patient expired 3 months later. Autopsy limited to the lungs was performed.
The left lung weighed 690 grams and the right lung 600 grams. The bronchi contained a small amount of frothy fluid bilaterally and had congested mucosa. The visceral pleural surfaces had a cobblestoned contour on the right and were roughened by extensive fibrous adhesions on the left. There were scattered areas of consolidation in both lungs. Sectioning the lungs revealed areas of firm tan-white fibrous tissue. The left lung parenchyma varied in color from red to gray to black, with areas of consolidation in the lower zone. The lungs exuded a moderate amount of frothy, bloody fluid on sectioning.
Two distinct morphologic processes were seen. The first was areas of fibrosis with numerous fibroblastic foci and foci of honeycombing. Nearby areas contained many neutrophils, macrophages, and lymphocytes. Multiple foci of hemorrhage and hemosiderosis were also identified.
The second process consisted of diffusely infiltrating and invading groups of cells with pleomorphic nuclei and prominent nucleoli making glands, in peripheral and central left upper and lower lobes, invading pleura, focally in central right middle and lower lobes. Additionally, these glands were found within pulmonary hilar lymph nodes. Immunohistochemical staining of the glands revealed strong positivity for CK7 and TTF-1, and negativity for CK20 and CDX-2.