Immunohistochemistry

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Author: Mikael Häggström [note 1]

Immunohistochemistry ordering

The main approaches to immunohistochemistry ordering are:

  • Look for a specified panel for the presentation at hand. For example, for an undifferentiated tumor with no clear lineage differentiation, an initial panel of CK, S100, vimentin and LCA can be used.[1]
  • Coming up with the most relevant differential diagnoses for the case at hand, and find the immunohistochemistry stains that best distinguish them. These can usually be found at the entries for each condition in Pathology Outlines, or you can pay for a subscription to ImmunoQuery[note 2], enter each differential diagnosis there, and have it generate the best immunohistochemistry panel.

Immunohistochemistry evaluation

The main methods for evaluating immunohistochemistry results are:

  • Looking up each differential diagnosis at for example Pathology Outlines and comparing their expected staining to see which entity is most likely.
  • Paying for a subscription to ImmunoQuery[notes 1], where you can enter immunohistochemistry results and generate a list of most likely conditions with that profile.

Preferably, immunohistochemistry results will be very specific or sensitive for a suspected condition, thereby confirming it if positive, or excluding it if negative, respectively. Even when that is not the case, immunohistochemistry can at least alter the likelihoods of different differential diagnoses. Pathology practice is too uncertain to perform calculations of exact percentages of likelihoods of differential diagnoses, but to demonstrate the general principle of how immunohistochemistry results are calculated, the following formula can be used:

  • Gross likelihood of a disease/condition = (Pre-test probability) x (Probability that the condition shows the immunohistochemistry results at hand).

The pre-test probability is a product of for example the incidence of the condition in the patient's epidemiologic type such as age and sex, as well as the probability that the condition would have caused the clinical course, including signs and symptoms, as well as the microscopic impression. For example, if you want to differentiate a pleomorphic liposarcoma from a pleomorphic rhabdomyosarcoma in soft tissue, you may find in ImmunoQuery that the following stains are most efficient in distinguishing the two, with the following percentages of being positive:

Soft tissue pleomorphic liposarcoma Soft tissue pleomorphic rhabdomyosarcoma
Desmin 17% 95%
Actin HHF-35 0% 71%

Let's say for example that your pre-test probability was about 30% for pleomorphic liposarcoma and 70% for pleomorphic rhabdomyosarcoma, that desmin stains positive, and actin HHF-35 stains negative in this case. Assuming that 0% positive rate means that 100% stain negative, the probability that pleomorphic liposarcoma shows these immunohistochemistry results at hand is:

  • 17% x 100% = 17%

The gross likelihood of pleomorphic liposarcoma therefore becomes:

  • 30% x 17% = 5.1%

In the same way, the corresponding gross likelihood of pleomorphic rhabdomyosarcoma is calculated as:

  • 70% x 95% x (100% - 71%) = 19%

As a result in this case, immunohistochemistry resulted in pleomorphic rhabdomyosarcoma going from about twice as likely compared to pleomorphic liposarcoma to about 4 times as likely.[notes 2]

General notes edit

Further reading:

Notes

  1. Cite error: Invalid <ref> tag; no text was provided for refs named ImmunoQueryCOI
  2. More detailed explanations about likelihood calculations on differential diagnoses in general can be read at:
    -Häggström, Mikael (2014). "An epidemiology-based and a likelihood ratio-based method of differential diagnosis ". WikiJournal of Medicine (Wikiversity Journal of Medicine) 1 (1). doi:10.15347/wjm/2014.002. ISSN 2002-4436. 
  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
  2. The author has no financial or other conflict of interest in the mentioning of ImmunoQuery.

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References

  1. Lin F, Liu H (2014). "Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. ". Arch Pathol Lab Med 138 (12): 1583-610. doi:10.5858/arpa.2014-0061-RA. PMID 25427040. Archived from the original. . 

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