The February 2011 Journal of Thoracic Oncology has the long-awaited new classification for lung adenocarcinoma. This paper is a MAJOR multidisciplinary achievement that aligns the interests, concerns, and expertise of pathologists, oncologists, surgeons, and radiologists. I can't think of another classification in any other organ system that has attempted this kind of collaborative effort or produced an audacious result. It is evidence-based and rationales for various critical decisions are clearly expounded.
One of the interesting asides is the questions posed by different specialty stakeholders. Studying this alone provides compelling insights into different perspectives on lung adenocarcinoma. As pathologists, we must appreciate and understand these perspectives to be effective participants in the care of these patients and remain relevant to the oncology team. Thus, there is a radical shift from the previous paradigm tumor classification meant mainly for pathologists:
The goal is not only longer to solely provide the most accurate diagnosis but also to manage the tissue in a way that immunohistochemical and/or molecular studies can be performed to obtain predictive and prognostic data that will lead to improvement in patient outcomes.
Here's my key points:
- Modified classification scheme for small biopsy/cytology specimens (Table 2)
- Incorporation of histochemical stains (mucin), IHC stains (TTF-1, p63), and molecular studies in classification--reflecting what we already do in practice, I might add
- Elimination of "bronchioloalveolar carcinoma" and replacement with adenocarcinoma-in situ including a size limitation of ≤3 cm (and insistence on total histologic examination)
- Introduction of term/concept of "minimally invasive" ADC defined as a discrete solitary lesion ≤3 cm with predominantly lepidic growth and ≤ 5 mm invasion in greatest dimension
- Definition of a new subtype, "lepidic predominant" ADC (LPA) for nonmucinous tumors with a predominantly lepidic growth pattern but with at least one focus of invasion > 5 mm
- For invasive ADC, semiquantitative subtyping into patterns in 5% increments based on "comprehensive histologic subtyping"--this incorporates previous work of Dr. Travis et al (see previous post)
- Re-classification of "formerly" mucinous BAC as invasive mucinous ADC, in recognition that the majority of these tumors demonstrate invasion--Table 4 is a nice summary of invasive mucinous ADC versus nonmucinous AIS/LPA
- Addition of enteric ADC as a recognized variant--these are the tumors that morphologically (and immunohistochemically CK7-,CK20+) resemble primary/metastatic colorectal ADC
- Re: small biopsies--"All current data that justify the importance of the distinction between histologic types of NSCLC in patients with advanced lung cancer are based on light microscopy alone." (my emphasis)
- Clearly stated considerations for "good practice" regarding judicious use and conservation of small biopsy specimens
- Very helpful algorithm for ADC diagnosis in small biopsy/cytology specimens
- Excellent table (5) summarizes associations between ADC subtypes, molecular patterns and radiographic appearance
There is also a nice summary of research questions for specifically for pathologists as well as clinical research questions related to the identification of prognostic and predictive markers/features.
One recommendation that was made in consideration of future molecular research is one I think is applicable not only with regard to future molecular studies but is crucial for all studies looking for prognostic and predictive markers: that these studies be based on "well-annotated clinical and pathologic datasets." My own personal experience with lung cancer research confirms this recommendation and I wholeheartedly agree. It is essential to carefully review all cases included in any retrospective study and I would propose that a histologic tool be developed for annotating cases prospectively to be entered in a database.