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  Table of Contents  
SPECIAL ARTICLE
Year : 2021  |  Volume : 58  |  Issue : 1  |  Page : 32-34
 

Advances in pathology in 2020: Year's roundup


Consultant Histopathologist, Columbia Asia Hospital Whitefield, Bangalore, India

Date of Submission15-Dec-2020
Date of Decision15-Dec-2020
Date of Acceptance19-Dec-2020
Date of Web Publication24-Mar-2021

Correspondence Address:
Sanjeev Vasudev Katti
Consultant Histopathologist, Columbia Asia Hospital Whitefield, Bangalore
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_1353_20

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How to cite this article:
Katti SV. Advances in pathology in 2020: Year's roundup. Indian J Cancer 2021;58:32-4

How to cite this URL:
Katti SV. Advances in pathology in 2020: Year's roundup. Indian J Cancer [serial online] 2021 [cited 2021 Apr 16];58:32-4. Available from: https://www.indianjcancer.com/text.asp?2021/58/1/32/311848




Literature is the most agreeable way of ignoring life.

- Fernando Pessoa, The Book of Disquiet

The Portuguese poet and philosopher clearly did not account for the contents of this year's medical literature, which has been awash with COVID-19-related studies reflecting the impact the pandemic has had on our lives. It has also, to some extent, led to a feeling of “Oh! Not this again” amid rising COVID-19 fatigue. An attempt has been made, in this brief roundup of pathology literature, to select a few non-COVID articles, which struck the author as interesting and relevant.

Things done well and with care, exempt themselves from fear

- William Shakespeare, Henry VIII

The Indian Journal of Cancer ran a series of articles[1],[2],[3],[4] this year on evidence-based approach to grossing of cancer resection specimens and it is only fair to start this write up with a mention of a commentary on “Macroscopy under the microscope – a critical appraisal of grossing techniques” published in Histopathology.[5] The authors highlight pertinent points related to macroscopic examination of specimens including inadequate or even complete lack of training of junior pathologists in grossing techniques by experienced pathologists, and complete disregard of discussion of macroscopic features in scientific meetings. Several practical issues faced in day-to-day practice are also discussed such as the impact of double-counting of lymph nodes in cancer resection specimens, particularly when the number of lymph nodes retrieved is used as a marker of the quality of surgery. Contentious guidelines that stipulate a minimum number of tissue sections to be submitted in different specimen types and the practical utility of including poorly reproducible and clinically insignificant data in the macroscopic description also get a mention.

Training in macroscopic examination and dissection should be treated on par with microscopy. Specimen sampling should be done meticulously and with care to obtain the most relevant information; however, the operator should use judgment in every individual case to select appropriate blocks.

A drop of ink may make a million think

- Lord Byron

The prognostic significance of harvesting adequate lymph nodes in colorectal cancer specimens is well recognized and several techniques to improve lymph node harvesting are already described.[6],[7],[8] The subject, however, continues to interest researchers and at least three related articles were published in reputed journals this year.[9],[10],[11] One of them, a study published in the Journal of Clinical Pathology – “Preoperative endoscopic tattooing technique improved lymph node retrieval in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy” deserves mention.[9] This was a retrospective case-control study that evaluated the utility of preoperative endoscopic tattooing in identifying and increasing the yield of small lymph nodes in the tumor-draining region. Using a multivariate Cox regression analysis, the authors concluded that preoperative tattooing improved lymph node yield independently of other clinicopathological variables. In contrast to similar previous studies,[12],[13],[14] it exclusively looks at rectal carcinomas post neoadjuvant chemoradiation (NACR), the group in which obtaining adequate lymph nodes is the most challenging. The technique not only improves the number of lymph nodes harvested but also aids the surgeon in delineating the tumor when there is near total tumor response to NACR.

Preoperative endoscopic tattooing is not only an easy and practical method to increase lymph node yield in rectal carcinoma following NACR but also acts as a guide to the surgeon in identifying the tumor bed.

We demand rigidly defined areas of doubt and uncertainty

- Douglas Adams, the Hitchhiker's Guide to the galaxy

There has been an explosion in the interest in assessing programmed death–ligand-1 (PDL-1) expression in various tumor types to predict tumor response to immunotherapy. However, reporting of PDL-1 immunohistochemistry is complicated by diverse scoring and reporting systems across multiple antibody clones, cancer types, and immunotherapy agents. For example, in non-small cell lung carcinoma (NSCLC), the PDL-1 inhibitor pembrolizumab is indicated if there is at least 1% tumor cell staining.[15] In contrast, in head and neck cancers, PDL-1 staining is assessed in both tumor cells and immune cells and a combined score of at least 1 is an indication for immunotherapy.[16] In urinary bladder cancers, the cutoff combined PDL-1 score for treatment with pembrolizumab is 10 and if atezolizumab is being considered, then PDL-1 is only assessed in immune cells with a cutoff of at least 5%.[17] The variable staining associated with different antibody clones further complicates interpretation and leads to high inter- and intraobserver variation.

In the article “Inter and intraobserver agreement of programmed death-ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma, and breast carcinoma”, Downes et al.[18] assess the consistency of reporting using various antibody clones (SP263, SP142, 22C3, E1L3N) in head and neck squamous cell carcinoma, urothelial carcinoma, and breast carcinoma.

The study highlights important issues on PDL-1 staining and reporting by pathologists. Although pathologists overall attained impressive levels of inter- and intraobserver agreement in PDL-1 scoring, the major sources of variable interpretation included the PDL-1 assay itself (e.g. the clone SP142 had the least agreement) and the scoring algorithms. Interpretation of PDL-1 staining in tumor cells had good agreement, but the scoring of PDL-1 in immune cells was challenging. Even though the degree of disagreement was only low to moderate, the rigid cutoff points for immunotherapy can mean potentially inappropriate treatment in individual patients.

It is possible that as data accumulates and the indications for immunotherapy either as a single agent or in combination with chemotherapy expand, the cutoff points will be adjusted to maximize clinical effectiveness, but until that time, pathologists reporting PDL-1 immunohistochemistry should be aware of the potential pitfalls and their implications.

Consistency in PDL-1 reporting can be achieved by adequate knowledge of clinical algorithms and cutoff points and also the differential impact of antibody clones in staining scores.

Tomorrow is another day

- Margaret Mitchell, Gone with the Wind

Immunohistochemistry (IHC) is widely used in surgical pathology. If a machine could predict the immunophenotype of individual cells based on routine hematoxylin and eosin (HE) staining, it would not only save money and time but also tissue consumed. Jackson et al.[19] in their interesting study performed HE staining on 12 slides and digitally registered the images before destaining and performing immunohistochemistry with SOX10. The second set of images were registered and then overlapped and compared with the HE images. Using color thresholding and machine learning techniques, a convolutional neural network was developed trained to predict SOX10 nuclear staining on HE stained whole slide images. The results of the virtual immunohistochemistry (vIHC) were promising showing good concordance with conventional IHC. However, the results were far from perfect with nonmelanocytic cells being frequently highlighted. Rarely, melanocytic cells were even missed. The authors admit that the study had multiple limitations in terms of registration of images, tissue warping during conventional IHC procedure, and the limited number of cases in the study. However, vIHC can prove to be a very useful tool if neural networks can be developed for multiple tissue and tumor types similar to a de novo IHC marker. Once such a model is created, several large-scale studies can be performed at no additional cost.

Machine learning technology and artificial neural networks are the future and will have a wide-ranging impact on the diagnosis and treatment of cancer patients.

Peer-review:

This article was peer-reviewed internally.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ambekar A, Rao V, Pai SA, Bindhu MR, Midha D, Kaushal S, et al. Grossing and reporting of testicular tumor specimens: An evidence-based approach. Indian J Cancer 2020;57:7-12.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Shet T, Pai T, Wadasadawala T, Nair N, Gulia S. Grossing and reporting of breast cancer specimens: An evidence-based approach. Indian J Cancer 2020;57:144-57.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Katti SV, Paulose RR, Malipatil B, Verma NS. Grossing and reporting of colorectal cancer resection specimens: An evidence-based approach. Indian J Cancer 2020;57:239-52.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Anila KR, Kainickal CT, Thomas S, Jayasree K. Grossing and reporting of squamous cell carcinoma of oral cavity-An evidence-based approach. Indian J Cancer 2020;57:378-87.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Varma M, Delahunt B, McCluggage WG, Shah VI, Berney DM. Macroscopy under the microscope: A critical reappraisal of grossing techniques. Histopathology 2020;76:930-3.  Back to cited text no. 5
    
6.
Horne J, Carr NJ, Bateman AC, Kandala N, Adams J, Silva S, et al. A comparison of formalin and GEWF in fixation of colorectal carcinoma specimens: Rates of lymph node retrieval and effect on TNM staging. J Clin Pathol 2016;69:511-7.  Back to cited text no. 6
    
7.
Abbassi-Ghadi N, Boshier PR, Goldin R, Hanna GB. Techniques to increase lymph node harvest from gastrointestinal cancer specimens: A systematic review and meta-analysis. Histopathology 2012;61:531-42.  Back to cited text no. 7
    
8.
Liu J, Huang P, Zheng Z, Chen T, Wei H. Modified methylene blue injection improves lymph node harvest in rectal cancer. ANZ J Surg 2017;87:247-51.  Back to cited text no. 8
    
9.
Chen YT, Wang JY, Wang JW, Chai CY. Preoperative endoscopic tattooing technique improved lymph node retrieval in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy. J Clin Pathol 2020;73:267-72.  Back to cited text no. 9
    
10.
Renshaw AA, Gould EW. How many lymph nodes are enough in a colorectal resection? Am J Surg Pathol 2020;44:1290-2.  Back to cited text no. 10
    
11.
Pitto F, Zoppoli G, Scabini S, Romairone E, Fiocca R, Ballestrero A, et al. Lymph node number, surface area and lymph node ratio are important prognostic indicators in neoadjuvant chemoradiotherapy treated rectal cancer. J Clin Pathol 2020;73:162-6.  Back to cited text no. 11
    
12.
Dawson K, Wiebusch A, Thirlby RC. Preoperative tattooing and improved lymph node retrieval rates from colectomy specimens in patients with colorectal cancers. Arch Surg 2010;145:826-30.  Back to cited text no. 12
    
13.
Bartels SAL, van der Zaag ES, Dekker E, Buskens CJ, Bemelman WA. The effect of colonoscopic tattooing on lymph node retrieval and sentinel lymph node mapping. Gastrointest Endosc 2012;76:793-800.  Back to cited text no. 13
    
14.
Kang J, Park HS, Kim I, Song Y, Baik SH, Sohn SK, et al. Effect of preoperative colonoscopic tattooing on lymph node harvest in T1 colorectal cancer. Int J Colorectal Dis 2015;30:1349-55.  Back to cited text no. 14
    
15.
FDA expands pembrolizumab indication for first-line treatment of NSCLC (TPS≥1%). FDA [Internet]. 2019 Dec 20 [cited 2020 Dec 12]; Available from: https://www.fda.gov/drugs/fda-expands-pembrolizumab-indication-first-line-treatment-nsclc-tps-1.  Back to cited text no. 15
    
16.
FDA approves pembrolizumab for first-line treatment of head and neck squamous cell carcinoma. FDA [Internet]. 2019 Dec 20 [cited 2020 Dec 12]; Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-first-line-treatment-head-and-neck-squamous-cell-carcinoma.  Back to cited text no. 16
    
17.
Suzman DL, Agrawal S, Ning Y-M, Maher VE, Fernandes LL, Karuri S, et al. FDA approval summary: Atezolizumab or pembrolizumab for the treatment of patients with advanced urothelial carcinoma ineligible for cisplatin-containing chemotherapy. Oncologist 2019;24:563-9.  Back to cited text no. 17
    
18.
Downes MR, Slodkowska E, Katabi N, Jungbluth AA, Xu B. Inter- and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma. Histopathology 2020;76:191-200.  Back to cited text no. 18
    
19.
Jackson CR, Sriharan A, Vaickus LJ. A machine learning algorithm for simulating immunohistochemistry: Development of SOX10 virtual IHC and evaluation on primarily melanocytic neoplasms. Mod Pathol 2020;33:1638-48.  Back to cited text no. 19
    




 

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