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This article serves as an introduction to anatomical pathology and discusses the basics.

Pathology simplified

H&E is the standard...

  • Too much PINK = DEAD (necrosis).
  • Too much BLUE = BAD.

In words:

  • Blue is bad and pink is dead![1]


  • Lymph nodes are very blue... they aren't necessarily bad.


Very common

  • Eosinophilic - pink.
  • Hyperchromatic - blue.

Less common

Nuclear destruction words

There are several fancy terms:[4]

  • Karyolysis = nuclear fading/dissolution.
  • Pyknosis = nuclear shrinkage.
  • Karyorrhexis = nuclear fragmentation.


DDx in medicine

Mnemonic CINE-TV-DATE:

  • Congenital.
  • Inflammatory.
  • Neoplastic.
  • Endocrine.
  • Trauma.
  • Vascular.
  • Degenerative.
  • Autoimmune.
  • Toxic.
  • Everything else (iatrogenic, idiopathic, psychiatric).

In diagnostic pathology, most stuff falls into the neoplastic category.

Basic pathologic DDx of malignancy

Germ Cell


  • Melanoma, i.e. malignant melanoma, is a separate category as it can look like almost anything under the microscope.

Factors to consider when attempting to group by morphology:

  1. Cell cohesion - dyscohesive vs. cohesive.
    • If one sees several groups of 5+ cells... probably cohesive.
  2. Cell size - in relation to a neutrophil or red blood cell.
  3. Cytoplasm - abundance (scant, moderate, abundant).
  4. Chromatin - coarseness (fine, granular).

Probable category by morphology:

  • Carcinoma = cohesive, relatively large (>~2X neutrophil), +/-nucleolus, +/-gland formation (circular structures), often moderate to abundant cytoplasm.
  • Sarcoma = cohesive, composed of spindle cells (cells taper at both ends, nucleus oval/cigar-shaped).
  • Germ cell tumour = appearance often similar to carcinoma.
  • Neuroendocrine carcinoma = cohesive, fine granular chromatin and no nucleolus.
  • Lymphoma = dyscohesive, relatively small (usually <=2X neutrophil diameter), usu. scant basophilic (blue) cytoplasm.
  • Melanoma = classically pigmented, often a prominent red nucleolus, a mix of spindle cells and epithelioid cells, mix of cohesive and dyscohesive cells.

Histomorphologic classification

Types of cells:

  • Spindle cell:
    • Tapered at both ends.[5]
    • Suggests mesenchyme, i.e. sarcoma, compatible with melanoma and some carcinomas.
  • Plasmacytoid cell.
    • Resemble a plasma cell: eccentric nucleus, "clockface" chromatin pattern, scant basophilic cytoplasm.
  • Epithelioid cell.
    • Looks like epithelium - cell borders touch neighbouring cells so that the cells collectively form a barrier.
  • Small round blue cell tumour:
    • Small cells with scant cytoplasm.

Finding the elements


  • Nucleus darker (hyperchromatic) - key feature.
  • No nuclear membrane - key feature.


  • Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.


  • Little dots = the multilobular nucleus - key feature.
  • Neutrophils are often found with friends, i.e. lymphocytes, plasma cells.

DDx of little specs:

  • Nuclear debris - apoptotic cell.
    • Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.


  • AKA PMNs - polymorphonuclearcyte, polymorphonuclear cell.
  • You find PMNs by their nucleus; on a histologic section don't bother looking for the cell membrane (they are usually impossible to see).
  • A collection of PMNs... think about necrosis and abscess.

Lymph node metstatsis

  • Take a good to look at the tumour first.
  • Tumour in a node is often better differentiated than the most poorly differentiated part in the primary site.
  • Subcapsular space - the first place to look for mets.
  • Lymph node metstasis are usually obvious.
  • Histiocytes may be difficult to separate from tumour - esp. initially.
    • Histiocytes usually are in germinal centre, i.e. the node architecture helps,
    • Malignant cells have to have malignant features, i.e. the NC ratio is abnormal, there is nuclear pleomorphism.

See: Lymph node article for a detailed description of cell types in a lymph node.

DDx of pink stuff (on H&E)

  • Collagen (fibrous tissue).
  • Amyloid.
  • Blood clot (organized).
  • Smooth muscle cells (SMCs).

Smooth muscle cells (SMCs) vs. fibrous tissue

Fibroblasts (fibrous tissue):

  • Wavy nuclei with pointy ends.
  • Less nuclei.


  • Elliptical nuclei.
  • More nuclei.

Remembering the above:

  • SMCs are stretched; ergo, not wavy.
  • Fibrous tissue is fibrous... more protein... less cells; ergo, less nuclei.
  • Fibroblast = football-like.
  • Cigar-shaped nuclei (SMCs) are affected by cigars (smoking causes vascular disease).


  • Schwann cells (found in nerve): nuclei = wavy appearance, thin. (???)

Signet ring cells


  • Signet ring cells resemble signet rings (image).
    • They contain a large amount of mucin, which pushes the nucleus to the cell periphery. The pool of mucin in a signet ring cell mimics the appearance of a finger hole and the nucleus mimics the appearance of the face of the ring in profile.


  • Typically 2-3x the size of a lymphocyte.
    • Smaller than the typical adipocyte.
  • Often have a cresentic-shaped nucleus, or ovoid nucleus.
    • Capillaries sectioned on their lumen have endothelial cells-- the nuclei of these are more spindled.
  • SRCs are usually close to friend (another SRC)
    • This helps differentiate SRCs from capillaries sectioned on their lumen.
  • The mucin is often clear on H&E... but maybe eosinophilic.


  • PAS stain.
  • Alican blue-PAS stain.


Comment: It has been said that there are two types of pathologists... those that have missed SRCs and those that will miss SRCs.


  • Granulomas can be elusive to the novice.
  • Plural of granuloma was granulomata; granulomas (an anglicized version) is, however, now generally accepted.

Definition of granuloma

  • Many definitions exist.
  • The term is used rather loosely by clinicans.
    • Radiologists occasionally call small lung nodules "granulomas".

Strict pathologic definition

Robbins definition:

  • Chronic inflammatory reaction characterized by the focal accumulation of activated macrophages, often with an epithelioid appearance.[6]
    • "Epithelioid" cells = cells whose morphology resembles that of epithelial cells; the cells appear to adhere to one another.

Adams definition - it's short & sweet:

  • A compact collection of macrophages.[7]
    • The macrophages must form a small ball/cluster of cells, i.e. touch one another.

Other pathologic definitions include the presence of:[7]

  • Plasma cells.
  • Lymphocytes.
  • Epithelioid macrophages.


  • The textbook answer for what is a granuloma is: "A collection of epitheliod macrophages."
    • Granulomas are often associated with lymphocytes.

Features that assist one in finding granulomas

Classification of granuloma

Broadly they can be divided (histologically) into:

  • Necrosing (also caseating).
    • More likely to be infectious.
    • Examples: Tuberculosis.
  • Non-necrosing.
    • Less likely to be infectious.
    • Examples: Crohn's disease, sarcoidosis, drug reaction.

Whether necrosis is present in a granuloma is affected by the immune function, e.g. a HIV/AIDS patient may have non-necrosing granulomata due to TB.


  • A few people differentiate between caseating (fragments of recognizable tissue) and necrosing (dead debris only).[8]
  • Infectious non-necrosing infections: Mycobacterium avium complex (MAC), cryptococcus, immunosuppressed individual.[8]

Etiologic classification of granulomas:

  1. Infectious, e.g. tuberculosis, MAC, fungal infection.
  2. Neoplastic, e.g. seminoma.
  3. Autoimmune, e.g. Wegener's granulomatosis, Churg-Strauss syndrome.
  4. Allergic, e.g. hypersensitivity pneumonitis.
  5. Foreign body, e.g. pulmonary talcosis.
  6. Drug reaction.
  7. Idiopathic, e.g. sarcoidosis.

Lung granulomata

There are many causes.[8]


  • Myocbacterial: Tuberculosis, MAC, other.
  • Fungal: Histoplasmosis, Cryptococcosis, Blastomycosis, Coccidioidomycosis.
  • Aspiration pneumonia.


  • Pneumoconioses/hypersensitivity pneumonitis: Talcosis, Berylliosis.


  • Sarcoidosis,
  • Wegener's granulomatosis,
  • Churg-Strauss disease,
  • Rheumatoid nodules.

Granular crap DDx

DDx of granular stuff:

  1. Lipofuscin - especially in old people.
  2. Hemosiderin.
  3. Bile - found in hepatocytes, yellow.
  4. Foreign material (tattoo pigment, anthracotic pigment).
  5. Melanin.


  • Granular stuff should prompt consideration of malignant melanoma.

Malignancy & inflammation

If there is lots of inflammation... and you're thinking cancer you should probably back-off, i.e. tend toward benign. Inflammation can make cells look more malignant than they might be if left alone.

Infectious stuffs


  • Staphylococcus - in clusters.
  • Streptococcus - in chains.


Basic knowledge of stain is important. The above article starts with H&E and goes from there.


Food and pathology

General surgeon talk

Generally, positive margins suck; in locally advanced rectal cancer survival, in one study, [9]five year survival was found to be 60%, 31% and 0% for R0, R1, and R2 resections respectively.

Oncologist talk

  • ECOG - score from 1-5 for performance status.[10]
    • ECOG = Eastern Cooperative Oncology Group.

ECOG score:

  • ECOG 0: healthy.
  • ECOG 1: ambulatory, no strenuous activity.
  • ECOG 2: limited to self-care in bed <50% of time.
  • ECOG 3: difficult to care for self in bed >50% of time.
  • ECOG 4: bed bound.
  • ECOG 5: dead.

Fixation & lifestyle

Pathologist have a great lifestyle 'cause tissue takes long to fix; the penetration of tissue by formalin is 1 mm/hour.[11]


  • Pathologists throw around the term high power field (HPF).
    • "HPF" has no agreed upon definition and, IMHO, should never be used without definition.

HPF generally refers to the area seen with the largest magnification objective (40x), i.e. the field at 400x (as the eye piece magnification is usually 10x). The field size varies significantly from microscope to microscope.

Estimating field of view

FOV = Deye piece x 1/Mobj.


  • FOV = field of view.
  • Deye piece = diameter of eye piece (this is usually inscribed on the side of the eye piece).
  • Mobj = magnification of the objective.


  • Deye piece = 22 mm
  • Mobj = 40x (largest magnification objective)

Applying the formula:

  • FOV = 22 mm / 40
  • FOV = 0.55 mm

Pathology reports

There is no universal standard but there is a push to standard.[12]

Standards lead to uniformity and consistency.[13]

The closest I've found to a standard is laid-out in by Goldsmith et al..[14]


As far as I know, the first papers on the topic of standards were written in 1992.[15][16][17]


The College of American Pathologists (CAP) has checklists for cancer - CAP protocols.

I suspect pathologists will use more checklists in the future... they are deemed effective in a number of places inside and outside of medicine. Surgeons know that checklists work and that they save lives.[18] Airline pilots have been using checklists for years and years.

An excellent book about checklists is: The checklist manifesto by Dr. Atul Gawande.[19]

Standard diagnostic notation

Site, operation/procedure:
- Tissue type diagnosis.

Gallbladder, cholecystectomy:
- Acute cholecystitis.


  1. Often said by STC.
  2. Storiform. URL: Accessed on: April 24, 2009.
  3. URL: Accessed on: March 9, 2010.
  5. URL: Accessed on: 18 January 2010.
  6. PBoD P.82.
  7. 7.0 7.1 Adams DO (1976). "The granulomatous inflammatory response. A review.". American Journal of Pathology 84 (1): 164–191. PMID 937513.
  8. 8.0 8.1 8.2 El-Zammar, OA.; Katzenstein, AL. (Feb 2007). "Pathological diagnosis of granulomatous lung disease: a review.". Histopathology 50 (3): 289-310. doi:10.1111/j.1365-2559.2006.02546.x. PMID 17257125.
  9. Larsen SG, Wiig JN, Dueland S, Giercksky KE (April 2008). "Prognostic factors after preoperative irradiation and surgery for locally advanced rectal cancer". Eur J Surg Oncol 34 (4): 410–7. doi:10.1016/j.ejso.2007.05.012. PMID 17614249.
  10. PMID 7165009.
  11. Gross rounds. 14 August 2009.
  12. URL:
  13. Leslie KO, Rosai J (November 1994). "Standardization of the surgical pathology report: formats, templates, and synoptic reports". Semin Diagn Pathol 11 (4): 253–7. PMID 7878300.
  14. Reporting guidelines for clinical laboratory reports in surgical pathology. Goldsmith JD, Siegal GP, Suster S, Wheeler TM, Brown RW. Arch Pathol Lab Med. 2008 Oct;132(10):1608-16. PMID 18834219.
  15. Rosai J, Bonfiglio TA, Corson JM, et al. (March 1992). "Standardization of the surgical pathology report". Mod. Pathol. 5 (2): 197–9. PMID 1574498.
  16. PMID 1574486
  17. Pubmed search
  18. Soar J, Peyton J, Leonard M, Pullyblank AM (2009). "Surgical safety checklists". BMJ 338: b220. PMID 19158173.
  19. Gawande A. The checklist manifesto: How to get things right. Metropolitan Books. 2009. URL: ISBN-13 978-0805091748.

External links