Adenocarcinoma of Mixed Histologic Type (pT1a) Arising in Usual Interstitial Pneumonia
Jeffrey L. Myers
University of Michigan
Ann Arbor, MI
A 79-year-old man presented for evaluation of a lung nodule. He had a history of
idiopathic pulmonary fibrosis, a diagnosis established 5 months prior to admission on the basis of
clinical and radiological abnormalities. He had experienced the insidious onset of shortness of breath
over the 4 months prior to his initial evaluation. At that time high resolution CT scan showed not only
diffuse abnormalities but also a 1.5 mass in the superior segment of his right lower lobe that enlarged
to 2 cms over a 5 month interval (see CT scan image). Other significant past medical history included
coronary artery disease for which he underwent bypass grafting three and a half years prior to admission.
He had smoked 1 pack of cigarettes per day for 13 years, but quit about 4 years prior to developing
respiratory symptoms. Pulmonary function studies showed a mild restrictive defect (FVC 68% of the
predicted value) with moderate impairment in gas exchange (DLCO 55% of the predicted value). He
underwent video-assisted thoracoscopic surgery and wedge biopsy of his right lower lobe.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
At low magnification
there is an adenocarcinoma with a variety of growth patterns including areas with bronchioloalveolar,
acinar, solid and micropapillary architecture. In some ares the adenocarcinoma merges with zones of
honeycomb change in which cystic air spaces are lined by non-neoplastic, ciliated respiratory epithelium.
On closer inspection there are foci in which there is an abrupt transition from non-neoplastic to
neoplastic epithelium. Away from the tumor there is patchy fibrosis that includes the aforementioned
honeycomb change. Combined with the patchy fibrosis this is strong evidence in support of usual
interstitial pneumonia (UIP).
The wedge biopsy and completion lobectomy of his right lower lobe showed a
peripheral tumor measuring 1.1 x 0.9 x 0.9 cms that abutted but did not invade visceral pleura. All
sampled N1 and N2 lymph nodes were free of tumor. Histologically his tumor shows a mixed pattern typical
of primary pulmonary adenocarcinomas comprising areas of bronchioloalveolar, acinar, micropapillary and
solid growth. While the diagnosis of adenocarcinoma is not challenging in this example, the diagnosis of
UIP is. He had a history of IPF but no definite diagnosis had been established. His preoperative CT
scan was described as showing, "lower lung predominant interstitial lung disease with interlobular septal
thickening, mild traction bronchiectasis and minimal groundglass opacities likely nonspecific
interstitial pneumonia (NSIP)." His wedge biopsy and subsequent lobectomy show a pattern of fibrosis
more typical of usual interstitial pneumonia (UIP). In the section available for your review the
fibrotic changes are overshadowed by the carcinoma, but demonstrate a patchy, subpleural and paraseptal
distribution characteristic of UIP. Elsewhere the "patchwork" distribution is combined with peripheral
architectural distortion in the form of subpleural honeycomb change and scarring. Rare subepithelial,
interstitial foci of proliferating fibroblasts and myofibroblasts (fibroblast foci) typical of UIP are
also present. This combination of findings establishes a diagnosis of UIP in a patient with the syndrome
Adenocarcinoma of mixed histologic type (pT1a) arising in usual interstitial pneumonia.
Carcinoma is a well recognized complication of UIP and accounts for around 20% of
The preponderance of evidence indicates that patients with UIP are at
increased risk of developing lung carcinoma and that the risk may be confounded by the prevalence of
Men account for about 90% of patients in retrospective observational studies.
Affected patients are also likely to be older, with an average age at carcinoma diagnosis of 65
to 75 years, and over 90% have a smoking history.
A substantial number of patients may not be
known to have IPF at the time that they undergo lung cancer surgery, a finding emphasized by several
authors including an abstract presented in poster form by Schmidt and associates at this year's annual
Squamous cell carcinoma is over represented in patients with UIP-associated lung
carcinomas. In surgical series published since 2000, squamous cell carcinoma accounts for just over 47%
UIP-associated carcinomas are more likely to be peripherally located and are
frequently situated within areas of lung fibrosis. In an abstract presented at this year's USCAP meeting
Dr. Lunardi and colleagues suggest that squamous cell carcinoma antigens (SCCA)-1/2 (SERPIN B3/B4) may
play a role in modulating both lung fibrosis and aberrant epithelial proliferation. 
Review of the Literature/Treatment Options (if applicable):
Patients with UIP who undergo surgical
resection for lung carcinomas experience higher rates of post-operative complications and hospital
There is no single factor that predicts which UIP patients are at greatest risk for
developing postoperative respiratory failure. Overall survival in UIP patients with early stage
carcinoma is worse than patients with comparable stage lung cancer who lack UIP.
Carcinoma is an important and frequently fatal complication in patients with UIP.
Having carcinoma with underlying UIP is an important risk factor that predicts not only a poor prognosis
but also higher morbidity from various treatment strategies. It is important to identify UIP in non-
neoplastic lung, something that may be more common than previously understood especially in older men.
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