Basics

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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]

Note:

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

Terms

Staining

Morphologic patterns

Name of pattern Meaning DDx (incomplete/abbrev. list) Image
Hobnail basement membrane area < area exposed to luminal surface angiosarcoma, clear cell carcinoma angiosarcoma - high mag. (WC)
Storiform spiral appearance or cartwhell pattern[5] solitary fibrous tumour, DFSP, dermatofibroma, UPS DFSP - intermed. mag. (WC),SFT - intermed. mag. (WC)
Fascicular the long axis of the (spindle) cells are perpendicular to one another in adjacent bundles of cells leiomyoma, leiomyosarcoma leiomyosarcoma - intermed. mag. (WC), Hemangiopericytoma (upenn.edu)
Plexiform web-like formation[6] plexiform neurofibroma, MPNST, plexiform lesion of pulmonary hypertension plexiform lesion of Pulm. HTn (flickr.com)
Cribriform pierced with small holes[7] cribriform DCIS, cribriform HGPIN, cribriforming in a tubular adenoma with high-grade dysplasia, endometrioid endometrial carcinoma cribriform DCIS (breastpathology.info)[8]
Solid or Sheeting no architecture - back-to-back cells with no pattern apparent / no spaces between cells solid DCIS, poorly-differentiated carcinoma solid DCIS (breastpathology.info)[8]
Micropapillary nipple like projections without a fibrovascular core (papillary = nipple-like[9]) micropapillary DCIS, micropapillary HGPIN micropapillary DCIS (breastpathology.info)[8]
Papillary nipple-like projection with a fibrovascular core papillary thyroid carcinoma papillary RCC - high mag. (WC)
Flat board-like, does not have a projection above the surface flat DCIS flat DCIS 1 (breastpathology.info),[8] flat DCIS 2 (breastpathology.info)[8]
Herring bone like herring bone (technique) for climbing a hill in cross country skiing; books on a shelf, where they have partially fallen over -- on the one shelf to the left and the one below to the right fibrosarcoma, synovial sarcoma, MPNST MPNST intermed. mag.(WC), MPNST - high mag.(WC)
Trabecular or cords trabecula = little beam[10]; quasi-linear arrangement of cells normal liver lobule, Sertoli cell tumour Sertoli cell tumour - low mag. (WC), PTC - intermed. mag. (WC).
Nested (nesting) islands of cells with a circular outline neuroendocrine tumours neuroendocrine tumour - low mag. (WC)
Biphasic / multiple patterns multiple patterns or cell types; e.g. spindle cells and epithelioid cells synovial sarcoma, malignant melanoma, pleomorphic adenoma, angiomyolipoma, chondroid syringoma DSRCT - high mag. (WC)

Nuclear destruction words

There are several fancy terms:[11]

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

Image:

Erosions and ulcers

  • Ulcer = lesion through skin or mucous membrane.
  • Erosion = limited to the mucosa - superficial ulceration.
    • In dermatopathology - through the epidermis.

Image:

Microscopic - erosion

Features - require 1 and 2:

  1. Loss of epithelium.
  2. Vital response at site of lost epithelium.

Image:

The general differential diagnosis

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.

Features of malignancy

Cytologic features of malignancy

It is said that:[13]

  1. It is the nuclear abnormalities that make a cell malignant.
  2. The cytoplasm that gives one clues as to the cell of origin.

Nuclear features and malignancy:[13]

Feature Strength in predicting malignancy?
Large nuclear size weak
Nuclear-to-cytoplasmic ratio strong
Nuclear pleomorphism weak
Nucleoli shape (angulated, spiked, complex) strong
Nucleoli size weak - generally; strong if like in a RS cell
High nucleoli number weak negative; finding favours benign
Chromatin hyperchromasia weak
Chromatin granularity strong
Nuclear membrane irregularities strong (clefting, flat edges, sharp angles),
scalloped (suggests benign)
Mitoses weak §
Atypical mitoses strong

§ mitoses are seen in poorly differentiated tumour and regeneration. High mitotic rate in the context of unremarkable nuclear morphology is usually not malignant.

Other features

In the context of soft tissue lesions, it is said that the two most important features of malignancy are:

  1. Necrosis.
  2. High vascularity.

Notes:

  • Benign soft tissue lesions may have marked nuclear atypia and abundant mitotic activity.

Basic pathologic differential diagnosis of malignancy

This should always be considered:

 
 
 
Malignancy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary
 
 
 
Metastatic

Q. Why?
A. (1) The site of the tumour can considerably change the differential diagnosis. (2) The management is usually totally different.

A clinically motivated histomorphologic classification of malignancy:

 
 
 
 
 
 
 
 
 
 
Malignancy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Epithelial
(Carcinoma)
 
Mesenchymal
(Sarcoma)
 
Germ cell
tumour
 
Neuroendocrine
carcinoma
 
Hematologic
 
Malignant
melanoma

Notes:

Morphologic grouping

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.
    • Presence of cell cohesion strongly disfavours lymphoma.
  2. Cell size - in relation to a neutrophil or red blood cell.
  3. Cytoplasm - abundance (scant, moderate, abundant).
    • Eosinophilic cytoplasm disfavours lymphoma.
  4. Chromatin - coarseness (fine, granular).
  5. Nucleoli - number (absent, present, multiple).
    • Large nucleoli (nucleoli seen with the 10x objective) pretty much exclude neuroendocrine.

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.

Dyscohesive vs. cohesive

Deciding cells are dyscohesive vs. cohesive is important, as it is a strong determinant of whether one is dealing with a lymphoid lesion or not.

Cell spacing Cell membrane Cytoplasm, abundance Cytoplasm, staining
Cohesive equal spacing or 3-D clusters or intracellular bridges visible & opposed (in >50% of cells) scant to abundant any
Dyscohesive unequal spacing, thin space surrounds cell not apparent usually scant usually basophilic
Value/utility equal or 3-D clusters suggests cohesive, pericellular space/rim suggests dyscohesive visible opposed membrane r/i cohesive abundant usu. cohesive eosinophilic usu. cohesive

Strong predictors of cohesive:

  • Intracellular bridges.
  • 3-D clusters.
  • Nuclear moulding.

Weak predictors of cohesive:

  • Eosinophilic cytoplasm.
  • Abundant cytoplasm.
  • >2 X RBC diameter (most lymphoma smaller).

Weak predictors of dyscohesive:

  • Pericellular space/rim.
  • Scant cytoplasm.
  • Basophilic cytoplasm.

Histomorphologic classification

Types of cells:

  • Spindle cell:
    • Tapered at both ends.[14]
    • Suggests mesenchyme, i.e. sarcoma, compatible with melanoma and some carcinomas.
  • Plasmacytoid cell.
    • Resemble a plasma cell: eccentric nucleus, moderate basophilic cytoplasm, +/-"clockface" chromatin pattern (clumping of chromatin at the periphery of the nucleus), +/-perinuclear hof (crescentic cytoplasmic clearing adjacent to the nucleus; represents abundant Golgi apparatus).
  • Epithelioid cell.
    • Looks like epithelium - cell borders touch neighbouring cells so that the cells collectively form a barrier.
  • Small round blue cell tumour/lymphoid:
    • Small cells with scant cytoplasm.
      • "Small" is classically 2x a "resting lymphocyte" diameter.
        • Diameter of a "resting lymphocyte" ~ diameter of a red blood cell (RBC) ~ 8 micrometres.
        • Most carcinoma cells are 3-4x the size of a RBC.
  • Small lymphoid (small cell lymphoma).
    • "Small" in the context of lymphoid is classically ~1x a "resting lymphocyte" diameter.
    • Often not malignant by cytology.

Differential diagnosis by site

Main article: Short power list

It is essential to have a concept of what is common. The short power list gives a short differential diagnosis for the common sites.

Main article: Long power list

The long power list is a longer list for the common sites.

Finding the elements

Mitoses

  • Nucleus darker (hyperchromatic) - key feature.
  • No nuclear membrane - key feature.
  • In prophase chromatin may have a scalloped border/beaded border.[15]

DDx:

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

Images:

Phases of mitosis

  • Prophase - chromatin condenses to chromosomes.
  • Metaphase - chromosome aligned.
  • Anaphase - spindles separated.
  • Telophase - reversal of prophase.

Neutrophils

Main article: Neutrophils
  • 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.

Notes:

  • 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

Main article: Lymph node metastasis
  • 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 - especially for the novice.
    • Histiocytes may be found in the germinal centres, i.e. the node architecture helps.
    • Malignant cells, generally, have to have malignant features, i.e. the NC ratio is abnormal, there is nuclear pleomorphism.
  • Several things can mimic metastases - see Lymph node metastasis.

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

Signet ring cell carcinoma

Main article: Signet ring cell carcinoma
  • It has been said that there are two types of pathologists... those that have missed SRCs and those that will miss SRCs.

Microscopic:

  • Cells resemble signet rings:
    • 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.
    • The nucleus mimics the appearance of the face of the ring in profile.
  • Cells typically 2-3x the size of a lymphocyte.
    • Smaller than the typical adipocyte.
  • Often have a crescent-shaped 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.

DDx:

  • Fat atrophy.

Stains:

  • PAS stain.
  • Alican blue-PAS stain.

Images:

Necrosis

Main article: Necrosis

Features:

  • Dead cells - pink (on H&E).
    • Anucleate cells ("Ghost cells")/outlines of cells - usu. subtle.
      • Fluffy appearance.
  • +/-Neutrophils (very common).

DDx of necrosis:

  • Fibrin.

Images (necrosis):

Granulomas

  • 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.[17]
    • "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.[18]
    • The macrophages must form a small ball/cluster of cells, i.e. touch one another.

Other pathologic definitions include the presence of:[18]

  • Plasma cells.
  • Lymphocytes.
  • Epithelioid macrophages.

Notes:

  • 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

  1. Collection of cells that have abundant bubbly cytoplasm - most useful feature.
  2. Multinucleated giant cells - these are easy to identify if you've seen some before.
  3. Necrosis - too much pink (on H&E stained sections).

Notes:

  • Small round collection of lymphocytes - without a capsule (as seen in lymph nodes).
    • If there are no macrophages... it's a lymphoid nodule.

As a list

Features:[19]

  1. Foamy/bubbly cytoplasm, abundant - low power.
  2. Epithelioid morphology - cell borders near indistinct - key feature.
  3. "Footprint" pattern nuclei/bean-shaped nuclei - key feature.
    • Macrophages usu. have an ovoid nucleus.
  4. +/-Nucleoli, small.
  5. +/-Fibrosis.
  6. +/-Palisading at edge.

DDx

  • Reactive germinal centre - especially if there are abundant surrounding lymphocytes.[20]

Classification of granuloma

Histologic classification

  1. Necrosing (also caseating).
  2. 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.

Notes:

  • A few people differentiate between caseating (fragments of recognizable tissue) and necrosing (dead debris only).[21]
  • Infectious non-necrosing infections: Mycobacterium avium complex (MAC), cryptococcus, infections in immunosuppressed individuals.[21]

Etiologic classification

  1. Infectious, e.g. tuberculosis, MAC, leprosy, syphilis, cat-scratch disease, schistosomiasis,[22] fungal infection.
  2. Neoplastic, e.g. seminoma, Lennert lymphoma,[23] ruptured ovarian teratoma.[24]
  3. Autoimmune/inflammatory, e.g. Wegener's granulomatosis, Churg-Strauss syndrome.
  4. Allergic, e.g. hypersensitivity pneumonitis.
  5. Foreign body, e.g. pulmonary talcosis, silicosis, berylliosis.[22]
  6. Drug reaction.
  7. Idiopathic, e.g. sarcoidosis.

Notes:

  • Memory device: DNF AAII = drug reaction, neoplasm, foreign body, allergy, autoimmune, idiopathic, infection.
  • A long DDx for granulomas is complied by James.[25]

Lung granulomata

There are many causes.[21]

Infectious:

Non-infectious:

Idiopathic/autoimmune:

Special granulomas

Fibrin ring granuloma

  • Classically associated with Q fever.
    • DDx:[26] infections (Coxiella burnetii (causes Q fever), CMV, EBV + others), drug reaction, malignancy (e.g. Hodgkin lymphoma[27]).
  • Appearance:
    • Epithelioid macrophages (i.e. a granuloma) surrounding a fibrin ring with a clear (lipid-filled) vacuole at its center.

Common morphologic problems

DDx of pink stuff (on H&E)

The ABCs of pink:

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

Images:

Smooth muscle cells (SMCs) vs. fibrous tissue

Fibroblasts (fibrous tissue):

  • Wavy nuclei with pointy ends.
  • Less nuclei.

SMCs:

  • 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).

Notes:

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

DDx of (brown) granular crap

DDx of granular stuff/pigment:

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

Notes:

  • Granular stuff should prompt consideration of malignant melanoma.
  • Memory device BH MILF = Bile, Homogentisic acid, Melanin, Iron (hemosiderin), Lipofuscin, Foreign material.
  • Homogentisic acid found in alkaptonuria,[28]can be considered the sixth (black) pigment.
    • Gentisic = jen-TIS-ik.[29]

Stains that can help sort it out

Staining

Main article: Stains

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

Immunohistochemistry

Main article: Immunohistochemistry

If the special stains don't help... there is immunohistochemistry.

Food and pathology

Main article: Pathology and food


Tumour remaining

Main article: Surgical margins

R classification:[31]

  • "RX resection" = residual tumour cannot be assessed.
  • "R0 resection" = clean margin macroscopically & microscopically.
  • "R1 resection" = microscopic tumour left.
  • "R2 resection" = macroscopic tumour left.

Surgeons use this terminology. Essentially, it is the margin status. It is nice when the surgeon's assessment and the pathologist's are in agreement.

Note:

  • Generally, positive margins suck. For example, in locally advanced rectal cancer, in one study,[32] five year survival was found to be 60%, 31% and 0% for R0, R1, and R2 resections respectively.

Clinician talk

Performance status

  • ECOG - score from 1-5 for performance status.[33]
    • 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.

Pathology & pathologists

Fixation & lifestyle

Pathologist have a great lifestyle 'cause tissue takes long to fix; the penetration of tissue by formalin is 1 mm/hour.[34]

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.

Miscellaneous

Infectious stuffs

Main article: Microorganisms

Images: http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/Gram3.htm

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


Microscopes

Main article: HPFitis
  • Pathologists throw around the term high power field (HPF).
    • "HPF" has no agreed upon definition and, IMHO, should never be used without a non-ambiguous 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.

Where:

  • 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.

Example:

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

Applying the formula:

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

Note:

  • Most of the resident microscopes, at U of T, have an eye piece diameter of 22 mm. Therefore, the field diameter at 40 X is approximately 22 mm / 40 X ~= 0.55 mm and the field of view is pi/4*(0.55 mm)^2 = 0.2376 mm^2.

Pathology reports

Main article: Pathology reports

The key point in report writing is that the report should be precise, complete and easy-to-understand.

Standards

There is no universal standard; however, there is a push to standardize by the Association of Directors of Anatomic and Surgical Pathology,[35] among others.

Checklists

Main article: CAP checklists

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

Pathologists will probably 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.[36] Pilots have been using checklists since the 1930s.

Standard diagnostic notation

Site, operation/procedure:
- Tissue type diagnosis.


Example:
Gallbladder, cholecystectomy:
- Acute cholecystitis.

Lab talk

Tissue cutting terms - these often vary from lab-to-lab:[37]

  • Recut = cut off the top of the block.
  • Serial sections = make several cuts off the top of the block and look at all of 'em.
  • Level = trim the block ~30 micrometres --throw away trimmed tissue-- and then cut a section to look at.
  • Deeper = trim the block ~100 micrometres --throw away trimmed tissue-- and then cut a section to look at.

See also

References

  1. ↑ Often said by STC.
  2. ↑ URL:http://pancreaticcancer2000.com/page1.htm. Accessed on: 3 June 2010.
  3. ↑ URL: http://www.merriam-webster.com/medical/argyrophilic. Accessed on: 29 August 2011.
  4. ↑ URL: http://en.wiktionary.org/wiki/argyrophilic. Accessed on: 29 August 2011.
  5. ↑ Storiform. dictionary.com. URL: http://dictionary.reference.com/browse/storiform. Accessed on: April 24, 2009.
  6. ↑ URL: http://www.mondofacto.com/facts/dictionary?plexiform. Accessed on: March 9, 2010.
  7. ↑ URL: http://dictionary.reference.com/browse/cribriform. Accessed on: 8 August 2011.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 URL: http://www.breastpathology.info/Sloane/dcis.html. Accessed on: 8 August 2011.
  9. ↑ URL: http://dictionary.reference.com/browse/papillary. Accessed on: 8 August 2011.
  10. ↑ URL: http://dictionary.reference.com/browse/trabecula. Accessed on: 26 December 2010.
  11. ↑ http://upload.wikimedia.org/wikipedia/en/5/51/Nuclear_changes.jpg
  12. ↑ Arashiro, RT.; Teixeira, MG.; Rawet, V.; Quintanilha, AG.; Paula, HM.; Silva, AZ.; Nahas, SC.; Cecconello, I. (Jul 2012). "Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis.". Clinics (Sao Paulo) 67 (7): 705-10. PMC 3400158. PMID 22892912. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400158/.
  13. ↑ 13.0 13.1 S. Boerner. 12 September 2011.
  14. ↑ URL: http://www.medterms.com/script/main/art.asp?articlekey=25657. Accessed on: 18 January 2010.
  15. ↑ URL: http://www.microbehunter.com/wp/wp-content/uploads/2009/lily_prophase.jpg and http://www.microbehunter.com/2009/12/06/mitosis-stages-of-the-lily/. Accessed on: 3 November 2010.
  16. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/Com08/Com801-1-Diss.htm. Accessed on: 3 November 2010.
  17. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 82. ISBN 0-7216-0187-1.
  18. ↑ 18.0 18.1 Adams DO (1976). "The granulomatous inflammatory response. A review.". American Journal of Pathology 84 (1): 164–191. PMID 937513. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2032357/?tool=pubmed.
  19. ↑ GS. 26 January 2010.
  20. ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 170. ISBN 978-0443066573.
  21. ↑ 21.0 21.1 21.2 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.
  22. ↑ 22.0 22.1 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 47. ISBN 978-1416054542.
  23. ↑ Summers, TA.; Rush, W.; Aguilera, N.; Lupton, G. (Oct 2009). "Cutaneous involvement in the lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified (Lennert lymphoma). Report of a case and review of the literature.". J Cutan Pathol 36 Suppl 1: 25-30. doi:10.1111/j.1600-0560.2008.01203.x. PMID 19775391.
  24. ↑ Phupong, V.; Sueblinvong, T.; Triratanachat, S. (Nov 2004). "Ovarian teratoma with diffused peritoneal reactions mimicking advanced ovarian malignancy.". Arch Gynecol Obstet 270 (3): 189-91. doi:10.1007/s00404-003-0479-8. PMID 15526210.
  25. ↑ James, DG. (Aug 2000). "A clinicopathological classification of granulomatous disorders.". Postgrad Med J 76 (898): 457-65. PMID 10908370.
  26. ↑ Tjwa M, De Hertogh G, Neuville B, Roskams T, Nevens F, Van Steenbergen W (2001). "Hepatic fibrin-ring granulomas in granulomatous hepatitis: report of four cases and review of the literature". Acta Clin Belg 56 (6): 341–8. PMID 11881318.
  27. ↑ de Bayser L, Roblot P, Ramassamy A, Silvain C, Levillain P, Becq-Giraudon B (July 1993). "Hepatic fibrin-ring granulomas in giant cell arteritis". Gastroenterology 105 (1): 272–3. PMID 8514044.
  28. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 20. ISBN 978-1416054542.
  29. ↑ URL: http://dictionary.reference.com/browse/gentisic+acid. Accessed on: 11 January 2012.
  30. ↑ Kovi J, Leifer C (July 1970). "Lipofuscin pigment accumulation in spontaneous mammary carcinoma of A/Jax mouse". J Natl Med Assoc 62 (4): 287–90. PMC 2611776. PMID 5463681. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2611776/pdf/jnma00512-0077.pdf.
  31. ↑ URL: http://www.informedicalcme.com/colon-cancer/tnm-stage-groupings/. Accessed on: 27 March 2012.
  32. ↑ 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.
  33. ↑ Oken MM, Creech RH, Tormey DC, et al. (December 1982). "Toxicity and response criteria of the Eastern Cooperative Oncology Group". Am. J. Clin. Oncol. 5 (6): 649–55. PMID 7165009.
  34. ↑ Gross rounds. 14 August 2009.
  35. ↑ URL: http://www.adasp.org/papers/position/Standardization.htm
  36. ↑ Soar J, Peyton J, Leonard M, Pullyblank AM (2009). "Surgical safety checklists". BMJ 338: b220. PMID 19158173. http://bmj.com/cgi/pmidlookup?view=long&pmid=19158173.
  37. ↑ URL: http://www.mailman.srv.ualberta.ca/pipermail/patho-l/2002-July/016955.html. Accessed on: 18 October 2011.

External links

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