Page 27 - Delaware Medical Journal - November/December 2020

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Significant advances in clinical medicine and oncology have markedly enhanced our
understanding of the nature of small peripheral lung tumors, and this has subsequently led to improved therapy and, in some cases, enhanced survival statistics.
TECHNICAL AND CLINICAL ADVANCES
1 The introduction of spiral CT scanning or single breath-hold continuous scanning by W. Kalender in the late 1980s is a truly remarkable example of marrying novel engineering to state-of-the- art computers.
2 The Noguchi pathological classification of small peripheral lung adenocarcinomas and its later correlation with thin-section CT scan images.1
3 Computer software that is capable of analyzing subtle changes in the size and morphology of pulmonary nodules.
4 Refined techniques of transthoracic needle biopsy of pulmonary
lesions and small-sample cytologic analysis.
5 Increasing knowledge of follow- up strategies and timing for intervention.
6 Advances in surgical techniques; particularly limited resections and VATS — video-assisted thoracoscopic surgery.
Tumor biology matters greatly in the heterogeneous subtypes of small
adenocarcinomas of the lung. Some of these tumors that are seen as ground- glass opacities (GGOs) on CT scans may be very indolent, with doubling times measured in years, while some small solid (and some partially solid) tumors have the potential for early metastasis.2 These clinical observations set the framework for the management of small lung nodules. The size and, critically, the appearance of small lesions on initial CT scans, and whether there is a change on follow-up scans, are all factors that are predictive of recurrence-free survival.
HISTOLOGY
It’s helpful to review Noguchi’s exquisite classification of small lung tumors and equally enlightening to see how closely his description of small lung tumors matches what is viewed on thin-section CT scans of some lesions.
Two types of small lung tumors are unique to screening CT studies: GGOs and partly solid lesions, the latter
with a variable mix of ground-glass appearance and a solid component. GGOs are defined as hazy opacities that do not distort the underlying pulmonary architecture. Histology shows an air-containing (occasionally mucoid-filled) lesion, with tumor
cells lining the alveolar walls and growth in a lepidic fashion. GGOs correspond to Noguchi type A and B tumors; there is no stromal invasion, and these lesions are now classified as adenocarcinoma in situ (AIS).3 A number of reports in the literature have reported no lymph node spread with these lesions and 100% five-year survival after resection.3 Noguchi type C lesions correspond to partly solid small tumors, with the solid
component representing fibroblastic proliferation (desmoplasia); this heralds stromal invasion. These lesions are
now classified as minimally invasive adenocarcinomas (MIA). Lymph node spread is seen in 28% of these tumors.3
It is the management of these two subtypes of adenocarcinomas in particular that has challenged investigators (and also created controversy) involved in CT screening studies.
GRAHAM CENTER RESEARCH
Kattepogu and co-investigators in the September/October 2020 Delaware Medical Journal present a detailed retrospective study of 45 patients with subcentimeter lung cancers detected during low-dose CT screening studies at the Helen F. Graham Cancer Center & Research Institute.4 As the authors note, with so few patients, an analysis of the data is statistically limited. It is also important to note that the cases were collected between 1999 and 2015, a time interval in which the base of knowledge about small CT-detected lung cancers was rapidly evolving,
as were strategies for follow-up and the optimal timing for intervention. As other investigators have similarly reported, the Graham Center data confirms that the size of a small lung lesion matters — the larger the lesion, the higher the likelihood of malignancy.
It is most unfortunate that Kattepogu’s research does not include a breakdown of the adenocarcinomas into subtypes: AIS, MIA, and frankly invasive adenocarcinoma (IA), or an imaging subtyping into GGOs and part-solid GGOs. This information is critical for
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