Pathology for clinicians and medical students

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Author: Mikael Häggström [note 1]
Following are important points for everyone working clinically, and who may therefore be involved with pathology. Still, the main advice is to ask a pathologist if unsure about anything pathology-related.

Notice

Advance notice allows the pathologist to prepare accordingly.

  • Provide the main condition(s) or feature(s) that you want the pathologist to look for whenever feasible.
  • Whenever there is a specimen type or circumstances thereof that is presumably unusual, give advance notice to the pathology department so that they can prepare accordingly.
  • Advance notice also generally gives you a better reply to any questions, such as before a tumor conference rather than putting the pathologist on the spot during it.
  • For tumor specimens, state significant cuts or other iatrogenic disruptions in the vicinity of the tumor if they may otherwise be misinterpreted as tumor perforation.

Biopsy versus aspiration

Generally order biopsy rather than aspiration, unless you know from the pathology department that they approve of the latter for the purpose at hand. Even if there are studies of promising aspiration results for any particular purpose, such studies are generally performed by subspecialty enthusiasts in the subject at hand, and their expertise and enthusiasm is not to be compared to that of your local cytotechnicians and pathologists.

Sampling

For cystic lesions, it is generally the cyst lining that is most helpful for the pathologist to make an optimal diagnosis, especially if there are nodules on the lining. Likewise, for seemingly necrotic lesions, try to find adjacent viable material to sample.

Staples

Margins of a lobectomy. A stapled portion is being cut off from the true bronchial margin, in order to take sections for microscopy from the underlying tissue, which therefore will be a few millimeters more proximal on the specimen than the true margin.

If feasible, limit the amount of staples in essential diagnostic tissue if there is a limited amount thereof (as staples need to be removed before microtomy, and the removal may tear the tissue). If multiple staples are necessary on a surgical margin (such as both ends of an intestinal segment), keep in mind that the pathologist may have to cut away the entire stapled portion before taking sections, and therefore the section for microscopy is a few millimeters more proximal on the specimen than the true margin.

Fixation

Within an hour after removal from the body,[1] tissue samples should generally be placed in vessels with the correct fixing solution, with a volume that allows them to lie freely in the solution.[2] The standard fixation fluid is generally 10% neutral buffered formalin, which is roughly equivalent to 4% formaldehyde.[3]

The main exceptions to using formalin are mainly: edit

  • Intraoperative consultation. If a specimen has several parts, and you only want intraoperative consultations on some of them, hold the rest back to avoid potential delays. For all fresh specimens, communicate clearly (such as on a requisition form with the specimen) whether intraoperative consultation is requested or not.
  • Suspected crystals, such as a tophus or other specimen suspicious for gout versus pseudogout. These should be sent in alcohol or dry, since formalin will dissolve the crystals.
  • Suspected lymphoproliferative disorders, such as lymph nodes (or other lymphoid aggregates) with a suspicion of lymphoma, where samples are generally put in a special solution for flow cytometry.
  • Need for genetic testing, such as some cases of products of conception.
  • Cytology specimens, which are preferably sent fresh (such as in red top tubes) to be processed within a few hours. If processing may be after a few hours, put tubes on ice, or add 50% alcohol.[4]
  • Need for microbiology evaluation, mainly bacterial culture.  
  • Need for immunofluorescence, such as immune complex-mediated disease, where specific preservation will give better test sensitivity.[5]

If you don't know, and if you cannot soon get in touch with anyone who can guide you, specimens can generally be stored in a fridge in the meantime, even overnight if it is late (but make sure to follow-up as soon as possible in the morning). Until then, don't put the specimen in formalin and don't freeze the specimen. Further information: Fixation

Skin

When marking the orientation of specimens, including skins, make "air knots", away from the tissue so that the pathologist can conveniently remove it without potentially cutting through the tissue.

Orientation of skin excisions should generally be marked when there is a substantial likelihood of needing to excise further in a location where it is inconvenient to perform re-excision in all directions indiscriminately. On the other hand, skin lesions with a low to intermediate suspicion of cancer (such as dark skin focalities in general) can usually be excised unoriented with a close margin, allowing for a later extended excision in case the initial pathology shows a malignancy. Orientation can be made with one or two (one short and one long) sutures, designated lateral, medial etc, or o’clock positions. The direction of the margin marked by any suture should not be ambiguous (like on the border between two of them).

Report interpretation

  • Longer discussions in the report and/or the presence of "Correlate clinically" essentially mean that the pathologist is not sure. Still, "Correlate clinically" implies that the pathologist has hope that a specific diagnosis can be reached by considering the whole clinical picture.

Clinical pathology

  • When ordering vitamin D levels, generally order calcifediol (25-hydroxycholecalciferol) and/or 25-hydroxyergocalciferol, and not calcitriol (also known as 1,25-dihydroxycholecalciferol). The latter is reserved for specific endocrinology purposes.
  • Don't order HbA1c in a patient who was transfused in the last 3 months, and consider a recent transfusion if a patient has a surprisingly normal HbA1c. In such patients, a fructosamine (glycosylated albumin) level is an alternative that is unaffected by transfusion, and reflects blood sugar control over the previous couple of weeks.[6]
  • See also: Thirty five major recommendations on test ordering (Choosing Wisely initiative 2020)
  • When ordering platelets or red blood cells, the patient will generally be transfused faster if you abide by the recommended dosage (generally one dose at a time, followed by a blood test to see the effect), rather than ordering excess units. With excess units ordered, even the first unit might be held up until blood bank staff has looked into the case in order to approve or reject the additional units.

Notes

  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.

Main page

References

  1. . Breast pathology grossing guidelines. UCLA Health. Retrieved on 2021-09-09.
  2. Katarzyna Lundmark, Krynitz, Ismini Vassilaki, Lena Mölne, Annika Ternesten Bratel. Handläggning av hudprover – provtagningsanvisningar, utskärningsprinciper och snittning (Handling of skin samples - Instructions for sampling, cutting and incision. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-09.
  3. . Paraformaldehyde, Formadehyde and Formalin. Duke University. Retrieved on 2019-12-17.
  4. . How to send fluid and make good cytology slides. Tufts University.
  5. Mubarak M, Kazi Javed I, Kulsoom U, Ishaque M (2012). "Detection of immunoglobulins and complement components in formalin fixed and paraffin embedded renal biopsy material by immunoflourescence technique. ". J Nephropathol 1 (2): 91-100. doi:10.5812/nephropathol.7518. PMID 24475396. PMC: 3886135. Archived from the original. . 
  6. Jennifer E. Frank, MD. Post-transfusion HbA1c. ClinicalAdvisor.

Image sources