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A.G. Nicholson
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E04 - Lung Cancer Pathology Classification (ID 4)
- Event: WCLC 2013
- Type: Educational Session
- Track: Pathology
- Presentations: 1
- Moderators:E. Duhig, M.S. Tsao
- Coordinates: 10/28/2013, 14:00 - 15:30, Parkside 110 A+B, Level 1
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E04.2 - Squamous Cell Carcinoma (ID 388)
14:25 - 14:45 | Author(s): A.G. Nicholson
- Abstract
- Presentation
Abstract
Squamous cell carcinoma is one of the four common types of lung cancer, and is defined as a malignant epithelial tumour showing evidence of squamous differentiation in the form of keratinisation, intercellular bridging or both. The main purpose of a pathological classification is to produce clinically relevant subgroups, in addition being reproducible, thorough, dynamic, and globally applicable, and this talk summarises the current WHO classification and potential new parameters. Current morphological classification: Since the 1999 classification, the recognised variants have been being papillary, clear cell, small cell and basaloid. Pure primary basaloid carcinomas of the lung are rare and the current WHO (2004) classification classifies basaloid carcinomas as variants of large cell carcinoma when they lack evidence of squamous differentiation. When squamous differentiation is present, they are classified as basaloid variants of squamous cell carcinoma. Basaloid morphology has been shown to carry a poorer prognosis than poorly differentiated squamous cell carcinomas for stage I and II disease. Papillary squamous cell carcinomas tend to be endobronchial and most are staged as T1N0 with a 5‑year survival of over 60 percent, which may be due to early presentation at this location rather than the architectural pattern itself. With regard to small cell and clear cell variants, the last decade has seen virtually no publications. Indeed, the primary reason for recognising these variants is to avoid misdiagnosis as metastases or other subtypes of lung carcinoma. Therefore, with the exception of the basaloid variant that appears to carry a worse prognosis, especially given small cell and clear cell variants are cytological parameters, consideration should be given to their removal from the next WHO classification, as well as the papillary variant. Also, given the increased knowledge in relation to immunophenotyping, basaloid and basaloid variant of squamous cell carcinoma could potentially be collapsed into a single subgroup of squamous cell carcinoma. Potential new morphological subgroups: The last decade has seen publications suggesting an architectural classification termed "alveolar filling" pattern. One paper has shown 100% survival when this pattern is present, although the number of cases showing this as a pure pattern is very low, around 1-2%. A more recent paper has suggested that the percentage of alveolar filling (greater than 70%) was significantly associated with a better prognosis, arguing that in tumours less than 30 mm in maximum diameter, a minimally invasive category might be appropriate. Tumours with this predominance would likely be sufficiently frequent (near 25%) to be clinically useful, and more data are required to support its inclusion. Other histological parameters such as extent of background of lymphocytic infiltration and keratinisation do not seem to carry prognostic significance. Classification according to presentation and/or aetiological factors: Publications in the last decade have suggested that the frequency of peripheral squamous cell carcinomas is increasing, with a greater number of stage 1 patients having peripheral presentation, although there was no difference in survival in N0 disease when compared to central tumours in one paper (Funai K et al Am J Surg Pathol 2003:27;978-984) . Indeed, survival was better in N1 disease in central presenting tumours. The alveolar pattern of growth was seen within the peripheral group only. However, unlike adenocarcinomas where those that present peripherally may be never-smokers, nearly all peripheral squamous carcinomas appear to be either current or ex-smokers. The frequency of HPV being present in squamous cell carcinoma of the lung varies extensively in the literature. The same ‘high-risk’ subtypes of HPV for cervical carcinoma are found in invasive bronchial carcinomas. However, although data from oropharyngeal squamous cell carcinomas suggest HPV infection is associated with better prognosis, data in the lung are conflicting. There is also likely synergism between smoking and infection as the preferred site of entry for HPV is at squamo-columnar junctions, and the presence or absence of HPV is unlikely to be recommended as a parameter for subclassification. Pre-invasive lesions: Squamous lesions arising in the airways have been regarded as progenitors of squamous carcinoma for decades and basal cell hyperplasia and squamous metaplasia also likely represent earlier phases in the development of squamous carcinomas. The current WHO/IASLC classification tabulates methodology for such gradation, and the system is sufficiently reproducible for diagnostic usage. The sequence progresses from basal cell hyperplasia through squamous metaplasia and squamous dysplasia to carcinoma-in-situ. Immunohistochemistry and small biopsies: The past decade has seen increasing usage of immunohistochemistry to refine the diagnosis of non-small cell carcinoma, driven by the needs for more accurate subclassification in relation to chemotherapeutic agents. This is not part of the current (WHO 2004) classification, although is recommended for use in biopsies by the IASLC as well as the ATS and ERS in relation subclassifying biopsies hitherto called non-small cell carcinoma, not otherwise specified (NSCLC-NOS) (Travis et al. J. Thor. Oncol. 2011;6:244-85). Therefore, any biopsy with NSCLC showing keratinisation and/or intercellular bridges should be classified as squamous cell carcinoma and, in NSCLCs lacking these or other disciminating morphological features on biopsy, but showing immunohistochemical evidence of squamous differentiation (one or two of CK 5/6, P63, and P40 being the most commonly used antibodies for this purpose) should be classified as NSCLC, favouring squamous cell carcinoma on immunohistochemistry. Similar investigation should also be considered in resected large cell undifferentiated carcinomas. Molecular subtypes: There is a vast literature on the carcinogenesis of squamous carcinoma, in particular preinvasive lesions. However none have yet become part of pathology classification. In relation to targeted therapy for invasive squamous cell carcinoma, data are still primarily related to clinical trials, with low frequencies of identification. Therefore, although targets such as DDR2 show some promise, at present, there is insufficient data to warrant pathological classification of invasive squamous carcinoma in relation to specific genetic abnormalities. Conclusion: Unlike adenocarcinomas, there has not been much advance in the morphogical subtyping of squamous cell carcinoma. There has however been advance in immunophenotyping, especially in relation to NSCLC-NOS, and it is hoped that molecular classification may have a role to play in the next decade.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MTE04 - Submit Your Challenging Cases for Discussion & Debate! (ID 48)
- Event: WCLC 2013
- Type: Meet the Expert (ticketed session)
- Track: Pathology
- Presentations: 1
- Moderators:E. Duhig
- Coordinates: 10/28/2013, 07:00 - 08:00, Bayside 105, Level 1
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MTE04.1 - Submit Your Challenging Cases for Discussion & Debate! (ID 596)
07:00 - 07:30 | Author(s): A.G. Nicholson
- Abstract
- Presentation
Abstract
The purpose of this session is to allow delegates to bring cases for discussion in relation to unusual thoracic tumours, primarily related to the pathology but also in relation to clinical management of complex pathological cases. Respiratory medicine does not provide a huge volume of material for the diagnostic pathologist, but much of this is related to thoracic cancers and their differential diagnoses. This sometimes leads to a lack of experience in managing rare and complex cases and most pathologists will have an, albeit informal, link for specialist opinion to help in this instance. Indeed, it is now a recommendation in the United Kingdom that a pathway of referral is part of the multidisciplinary management of lung cancer patients. In the speaker’s experience, around 60% of referrals for complex cases relate to tumour pathology, and this is perhaps increasing with the relative decrease in biopsy for non-neoplastic diseases and increased interest in the subtyping of more common tumours. Cases referred for specialist opinion tend to breakdown into small lung biopsies, in particular asking the question, "is there enough evidence to call the biopsy definitively malignant?" This is, in particular, in relation to adenocarcinoma. Another common area is the differential diagnosis of mesothelioma, in particular in relation to spindle cell rather than epithelioid proliferations in the pleura. The third common area for referral is the "rare" tumour, where cases will often be sent because the referring pathologist has been no previous experience of the particular neoplasm. This process is not only of benefit to the referrer but also for the specialist as it allows accrual of potential new entities, an example being primary pulmonary myxoid sarcomas with EWSR1-CREB1 fusion where cases were collected over a period of 12 years from first sighting. Even within these groups, the pattern of referral has changed over the last two decades. Between 1995 and 2000, there were frequent referrals in relation to the differential diagnosis of pulmonary marginal zone lymphoma of MALT origin and reactive pulmonary lymphoid hyperplasia. Now that distinguishing criteria are much more established, these referrals are much rarer. However the last two years has seen an increase in referrals of non-small cell carcinoma, in relation to the need for further subtyping, with many of the cases being those with diverging immunophenotype. Little has been done to assess the value of specialist referral. However a review of personal experience of 50 cases affirmed diagnoses in 26/50 (52%) cases, revised in 16/50 (32%) and favoured diagnoses in 8/50. 80% of reports were deemed to have major clinical significance. Average (laboratory and pathologist) coast was £130.47 respectively (in 2009), excluding lymphoma investigations and corporate costs and current charges in the UK vary between £150 and £250 per case for slide/block reviews. The author would argue that the cost of referral appears is offset by a high level of definitive diagnosis, negating further investigation. Average turnaround time was 5 days, excluding those over holidays, with 80% reported within 7 days. Prolonged reporting times were mainly due to those referring not sending blocks or unstained slides, necessitating further despatch of material. There is also additional delay when cases require molecular analysis. With the advance of digital pathology, this has potential to facilitate and speed up external opinions, although is still in its infancy. This is because referrals often comprise numerous slides which are still quicker to send and review via the microscope than scan and then go through remotely. However, for single or small numbers of slides, the technology has greater potential. Finally, the question is often asked what happens when the putative specialists are unable to make a diagnosis. In the author’s experience, some are undiagnosable for practical reasons, such as poor fixation, whilst some are sufficiently complex and unusual that a further collective opinion from fellow specialists is obtained and fed back to the referring pathologist. This is often after much emailing and debate!Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
