Difference between revisions of "Lymph node pathology"

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*[[Tularemia]].
*[[Tularemia]].


Images:
====Images====
www:
*[http://www.webpathology.com/image.asp?case=386&n=1 Cat-scratch disease (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=386&n=1 Cat-scratch disease (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=2&Case=386 Cat-scratch disease - high mag. (webpathology.com)]
*[http://www.webpathology.com/image.asp?n=2&Case=386 Cat-scratch disease - high mag. (webpathology.com)]
*[http://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-_very_low_mag.jpg CSD - very low mag. - showing serpentine shaped microabscesses (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-b-_high_mag.jpg CSD - high mag. - showing neutrophilic abscesses (WC)].
Image:Cat_scratch_disease_-_very_low_mag.jpg | CSD - very low mag. - showing serpentine shaped microabscesses (WC)
Image:Cat_scratch_disease_-_low_mag.jpg | CSD - low mag. - showing serpentine shaped microabscesses (WC)
Image:Cat_scratch_disease_-b-_high_mag.jpg | CSD - high mag. - showing neutrophilic abscesses (WC)
</gallery>


===Stains===
===Stains===

Revision as of 05:19, 16 November 2013

This article deals with non-haematologic malignant, i.e. metastases, and non-malignant lymph node pathology. An introduction to the lymph node is in the lymph nodes article.

Haematologic malignancies (in lymph nodes) are dealt with in other articles - see haematopathology and lymphoma.

Overview

Clinical:

  • Lymphadenopathy.

Differential diagnosis:[1]

  • Infectious - fungal, mycobacterial, viral, protozoal (Toxoplasma), bacterial (Chlamydia, Rickettsia, Bartonella)).
  • Neoplastic - lymphoma, carcinoma.
  • Endocrine - hyperthyroidism.
  • Trauma.
  • Autoimmune - SLE, RA, dermatomyositis.
  • Inflammatory - drugs (phenytoin).
  • Idiopathic - sarcoidosis.

Overview in a table

Entity Key feature Other findings IHC DDx Image
Non-specific reactive follicular hyperplasia (NSRFH) large spaced cortical follicles tingible body macrophages, normal dark/light GC pattern BCL2 -ve infection (Toxoplasmosis, HIV/AIDS), Hodgkin's lymphoma image ?
Lymph node metastasis foreign cell population, usu. in subcapsular sinuses +/-nuclear atypia, +/-malignant architecture dependent on tumour type (see IHC) dependent on morphology, endometriosis (mimics adenocarcinoma), ectopic decidua (mimics SCC)
Error creating thumbnail:
CRC metastasis
Breast metastasis
Progressive transformation of germinal centers large (atypical) germinal centers poorly demarcated germinal center (GC)/mantle zone interfaces, expanded mantle zone IHC to r/o nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) NLPHL, follicular hyperplasia
Toxoplasmosis large follicles; epithelioid cells perifollicular & intrafollicular reactive GCs, monocytoid cell clusters, epithelioid cells IHC for toxoplasma NSRFH, HIV/AIDS, Hodgkin's lymphoma
Error creating thumbnail:
TL - low mag.
Kikuchi disease (histiocystic necrotizing lymphadenitis) No PMNs histiocytes, necrosis IHC for large cell lymphoma (CD30 + others) SLE (has (blue) hematoxylin bodies in necrotic areas), large cell lymphomas
HNL - very high mag.
Cat-scratch disease PMNs in necrotic area "stellate" (or serpentine) shaped microabscesses, granulomas B. henselae, Dieterle stain HIV/AIDS, NSRFH
Error creating thumbnail:
Cat scratch - very low mag.
Dermatopathic lymphadenopathy melanin-laden histiocytes histiocytosis S100+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells) cutaneous T-cell lymphoma
Kimura disease eosinophils angiolymphoid proliferation (thick-walled blood vessels with hobnail endothelial cells) IHC ? Langerhans cell histiocytosis, drug reaction, angiolymphoid hyperplasia with eosinophilia
Kimura disease - very high mag.
Langerhans cell histiocytosis abundant histiocytes with reniform nuclei often prominent eosinophilia S100+, CD1a+ Kimura disease (eosinophilia), Rosai-Dorfman disease
Rosai-Dorfman disease sinus histiocytosis emperipolesis (intact cell within a macrophage) S100+, CD1a- Langerhans cell histiocytosis
Systemic lupus erythematosus lymphadenopathy (blue) hematoxylin bodies necrosis, no PMNs IHC for large cell lymphoma (CD30 + others) Kikuchi disease, large cell lymphomas
Error creating thumbnail:
SLEL - high mag.
Castleman disease, hyaline vascular variant thick mantle cell layer with laminar appearance ("onion skin" layering) hyaline (pink crap), lollipops (large vessels into GC), no mitoses in GC IHC - to r/o mantle cell lymphoma mantle cell lymphoma, HIV/AIDS
Castleman disease, plasma cell variant thick mantle cell layer sinus perserved, interfollicular plasma cells, mitoses in GC HHV-8 HIV/AIDS image ?
Intranodal palisaded myofibroblastoma spindle cells with nuclear palisading RBC extravasation, fibrillary bodies with a central vessel "amianthoid fibers" SMA+, cyclin D1+ schwannoma
IPM - very high mag.

Follicular lymphoma vs. reactive follicular hyperplasia

Factors to consider:[2]

Reactive follicular
hyperplasia
Follicular lymphoma
Follicle location cortex cortex and medulla
Germinal center edge sharp/well-demarcated poorly demarcated
Germinal center density well spaced, sinuses open crowded, sinuses effaced/
compressed to nothingness
Tingible body
macrophages
common uncommon
Germinal center
light/dark pattern
normal abnormal

Lymph node metastasis

General

  • Determination of lymph node status is one of the most common indications for the examination of lymph nodes.
  • It is a good idea to look at the tumour (if available) ...before looking at the LNs for mets.
  • Lymph node metastasis, in the absence of other metastases, often up-stage a cancer from stage II to stage III.

Gross

  • Outside:
    • "Large" - size varies by site.
      • Neck >10 mm.[3]
    • Shape - round more suspicious than oval.
  • Sectioned:
    • White firm lesion with irregular border - classic appearance.
    • Non-fatty hilum.[3]

Microscopic

Features:

  • Foreign cell population - key feature.
    • Classic location: subcapsular sinuses.
  • +/-Cells with cytologic features of malignancy.
    • Nuclear pleomorphism (variation in size, shape and staining).
    • Nuclear atypia:
      • Nuclear enlargement.
      • Irregular nuclear membrane.
      • Irregular chromatin pattern, esp. asymmetry.
      • Large or irregular nucleolus.
    • Abundant mitotic figures.
  • +/-Cells in architectural arrangements seen in malignancy; highly variable - dependent on tumour type and differentiation.
    • +/-Gland formation.
    • +/-Single cells.
    • +/-Small clusters of cells.

Notes:

  1. Cytologic features of malignancy may not be present; some tumours, e.g. gallbladder carcinoma, do not always have overt cytologic features of malignancy.
    • The diagnosis is based on the fact that they are foreign to the lymph node and architecturally consistent with a well-differentiated malignancy.
  2. Lymph node metastases in sarcomas are uncommon; they are seen in <3% of cases.[4]
  3. Fatty lymph nodes (esp. fatty hilus[3]) are less likely to harbor metastases.[5]

DDx - mimics of metastatic disease:

Images

Mimics

Kaposi sarcoma

  • One of the few non-lymphoid primary lymph node tumours.[9]

Melanocytic nevi

See: Dermatopathic lymphadenopathy.
  • Benign melanocytic nevi can be found in lymph nodes.[9]

Progressive transformation of germinal centers

  • Abbreviated as PTGC.

Reactive follicular hyperplasia

General

  • Many causes - including: bacteria, viruses, chemicals, drugs, allergens.
    • In only approximately 10% can definitive cause be identified.[10]

Microscopic

Features:[11]

  • Enlarged follicles, follicle size variation - key feature with:
    • Large germinal centers (pale on H&E).
      • Mitoses common.
      • Variable lymphocyte morphology.
      • Tingible-body macrophage (large, pale cells with junk in the cytoplasm).
      • Germinal centers (GCs) have a crisp/sharp edge.
      • Normal dark/light variation of GCs; superficial aspect light, deeper aspect darker.
    • Rim of small (inactive) lymphocytes.

DDx:

Image: Normal lymph node (umdnj.edu).

IHC

Screening panel:

  • CD3.
  • CD5.
  • CD10.
  • CD20.
  • CD30.
  • CD15.

Others:

  • BCL2 -ve.

Diffuse paracortical hyperplasia

General

  • Benign.

Microscopic

Features:[11]

  • Interfollicular areas enlarged - key feature.
    • T cell population increased.
    • Plasma cells.
    • Macrophages.
    • Large Reed-Sternberg-like cells.

Sinus histiocytosis

General

  • Benign.
  • Non-specific finding.

Microscopic

Features:[11]

  • Sinuses distended with histiocytes - key feature.
  • Plasma cells increased.

DDx:

Sign out

  • The finding is often ignored; may be signed out as morphologically benign lymph nodes.

Kikuchi disease

  • AKA histiocytic necrotising lymphadenitis (HNL).[12]
  • AKA Kikuchi-Fujimoto disease.

General

  • Rare disease that may mimic cancer, esp. lymphoma.
    • May cause fever & systemic symptoms.[13]

Epidemiology:[13]

  • Usually <40 years old.
  • Asian.
  • Female:Male = 3:1.[14]

Treatment:

  • Usually self-limited.[13]
  • Oral corticosteroids.

DDx:

Micrograph

Features (the three main features - just as the name suggests):[15]

  • Histiocytes.
    • May be crescentic.
  • Necrosis (due to apoptosis) - paracortical areas.[13]
    • Necrosis without neutrophils - key feature.
  • Lymphocytes (CD8 +ve).
  • Plasmacytoid dendritic cells.

Notes:

  • Dendritic cell - vaguely resembles a macrophage:[16]
    • Long membrane projections - key feature.
    • Abundant blue-grey cytoplasm, +/- ground-glass appearance.
    • Nucleus: small, ovoid, usu. single nucleolus.

Images

www:

IHC

  • CD68 +ve.
  • CD8 +ve - usu. predominant.
  • CD4, CD20, CD3, and CD30 - mixed.
    • Done to excluded lymphoma; esp. large cell lymphomas;[17] should show a mixed population of lymphocytes.
  • Others:
    • CD56 -ve.

Systemic lupus erythematosus lymphadenopathy

General

Microscopic

Features:[18]

  • Necrosis.
  • Hematoxylin bodies (in necrotic foci).
    • Dark blue irregular bodies on H&E.

DDx:

Images

Castleman disease

  • AKA angiofollicular lymph node hyperplasia, giant lymph node hyperplasia.[19]
  • Abbreviated CD.

General

  • Benign.
  • Hyaline vascular variant - a pathology of the follicular dendritic cells.[20]

Classification

CD is grouped by histologic appearance:[21]

  1. Hyaline vascular (HV) variant (described by Castleman).
  2. Plasma cell (PC) variant.
    • Usually multicentric, may be unicentric.
    • Abundant plasma cells.
    • Associated with HHV-8 infection (the same virus implicated in Kaposi's sarcoma).

Notes:

  • The subclassification of CD is in some flux. Some authors advocate splitting-out HHV-8 and multicentric as separate subtypes.[23]

Microscopic

Hyaline-vascular variant

Features:[24][25]

  • Pale concentric (expanded) mantle zone lymphocytes - key feature.
    • "Regressed follicles" - germinal center (pale area) is small.
  • "Lollipops":
    • Germinal centers fed by prominent (radially penetrating sclerotic) vessels; lollipop-like appearance.
  • Two germinal centers in one follicle.
  • Hyaline material (pink acellular stuff on H&E) in germinal center.
  • Sinuses effaced (lost).
  • Mitoses absent.

Images

www:

Plasma cell variant

Features:[25]

  • Interfollicular sheets of plasma cells - key feature.
  • Active germinal centers - mitoses present.
  • Sinus perserved.

IHC

Hyaline-vascular variant:

Plasma cell variant:

  • HHV-8 +ve.

Cat-scratch disease

  • AKA Cat-scratch fever.

General

  • Infection caused Bartonella henselae,[26] a gram-negative bacilla (0.3-1.0 x 0.6-3.0 micrometers) in chains, clumps, or singular.[27]
  • Treatment: antibiotics.

Clinical

Features:[28]

  • Usually unilateral.
    • May be disseminated in individuals with immune dysfunction.
  • Contact with cats.

Micrograph

Features:[28]

  • Necrotizing granulomas with:
    • Neutrophils present in microabscess (necrotic debris) - key feature.
      • Microabscesses often described as "stellate" (star-shaped).
  • +/-Multinucleated giant cells.

Notes:

  • May involve capsule or perinodal tissue.

DDx of stellate abscess in lymph nodes - cat split:[29]

Images

www:

Stains

  • Warthin-Starry stain +ve.

IHC

  • B. henselae IHC stain +ve - diagnostic.

Toxoplasma lymphadenitis

General

  • Caused by protozoan Toxoplasma gondii.

Microscopic

Features:[28]

  • Reactive germinal centers (pale areas - larger than usual).
    • Often poorly demarcated - due to loose epithelioid cell clusters at germinal center edge - key feature.
  • Epithelioid cells - perifollicular & intrafollicular.
    • Loose aggregates of histiocytes (do not form round granulomas):
      • Abundant pale cytoplasm.
      • Nucleoli.
  • Monocytoid cells (monocyte-like cells) - in cortex & paracortex.
    • Large cells in islands/sheets key feature with:
      • Abundant pale cytoplasm - important.
      • Well-defined cell border - important.
      • Singular nucleus.
    • Cell clusters usually have interspersed neutrophils.

Images:

Notes:

  • Monocytoid cells CD68 -ve.

IHC

  • IHC for toxoplasmosis.

Dermatopathic lymphadenopathy

General

  • Lymphadenopathy associated with a skin lesion - key feature.
  • May be benign or malignant (e.g. T-cell lymphoma).

Microscopic

Features:[30]

  • Abundant histiocytes & special histiocytes - in loose irregular clusters - located in the sinuses, i.e. sinus histiocytosis - key feature:
    • Do not form granuloma; may be similar to toxoplasma.
  • Plasma cells (medulla).
  • Eosinophils.

Histiocytes & special histiocytes:

  • Histiocytes:
    • +/-Melanin pigment key feature (if present).
    • Lipid-laden macrophages.
  • Interdigitating dendritic cells:
    • Need IHC to identify definitively.
  • Langerhans cells:
    • Classically have a kidney bean nuclei.
    • Need IHC to identify definitively.

DDx:

Images

IHC

  • Interdigitating dendritic cells: S100 +ve, CD1a -ve.
  • Langerhans cells: S100 +ve, CD1a +ve.

Kimura lymphadenopathy

Microscopic

Features:

  • Abundant eosinophils.
  • Thick-wall blood vessels.

Rosai-Dorfman disease

  • Abbreviated RDD.

General

  • AKA sinus histiocytosis with massive lymphadenopathy, abbreviated SHML.[31]
  • Super rare.
  • Prognosis - good.

Microscopic

Features:

  • Sinus histiocytosis:
    • Histiocytes - abundant.
      • Singular large round nuclei[32] ~2x the size of resting lymphocyte.
        • Prominent nucleolus - visible with 10x objective.
      • Abundant cytoplasm.
  • Emperipolesis (from Greek: em = inside, peri = around, polemai = wander about[33]):
    • Histiocytes contain other whole cells: neutrophils, lymphocytes, plasma cells.
      • The "eaten" cell is within a vacuole;[34] thus, it should have a clear halo around it.
      • Thought to be related to peripolesis; the attachment of a cell to another.[35]

DDx:

Images

www:

IHC

  • CD68 +ve.
  • S100 +ve.
    • Useful for seeing emperipolesis.
  • CD1a -ve.
    • CD1a positive in Langerhans cell histiocytosis.

Langerhans cell histiocytosis

Microscopic

Features:

  • Langerhans cells histiocytes - key feature.
    • Clusters of cells (histiocytes) with a reniform (kidney-shaped) nucleus and abundant foamy cytoplasm.
  • +/-Eosinophils - often prominent.

See Langerhans cell histiocytosis for details.

Lymph node hyalinization

  • AKA hyalinized lymph node.

General

  • Benign.
  • Associated with aging.[36]

Microscopic

Features:

  • Hyaline material (acellular pink stuff on H&E) within a lymph node.

Subdivided into:[36]

  • Mediastinal-type.
    • Usually in medullary sinus.
    • Onion peel-like appearance.
  • Pelvic-type hyalinization.
    • Discrete round, eosinophilic, glassy appearance at low power, whirled/fibrous at high power.
    • +/-Calcification.

DDx:

  • Amyloidosis - cotton candy-like appearance, usu. no calcifications.

Images:

See also

References

  1. URL: http://path.upmc.edu/cases/case289.html. Accessed on: 14 January 2012.
  2. DB. 4 August 2010.
  3. 3.0 3.1 3.2 Mack, MG.; Rieger, J.; Baghi, M.; Bisdas, S.; Vogl, TJ. (Jun 2008). "Cervical lymph nodes.". Eur J Radiol 66 (3): 493-500. doi:10.1016/j.ejrad.2008.01.019. PMID 18337039.
  4. Fong, Y.; Coit, DG.; Woodruff, JM.; Brennan, MF. (Jan 1993). "Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients.". Ann Surg 217 (1): 72-7. PMC 1242736. PMID 8424704. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1242736/.
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  15. URL: http://www.ispub.com/journal/the_internet_journal_of_head_and_neck_surgery/volume_1_number_1_30/article_printable/kikuchi_s_lymphadenitis_in_a_young_male.html. Accessed on: 1 June 2010.
  16. URL: http://www.healthsystem.virginia.edu/internet/hematology/hessedd/benignhematologicdisorders/normal-hematopoietic-cells/dendritic-cell.cfm?drid=214. Accessed on: 3 June 2010.
  17. Good DJ, Gascoyne RD (August 2009). "Atypical lymphoid hyperplasia mimicking lymphoma". Hematol. Oncol. Clin. North Am. 23 (4): 729–45. doi:10.1016/j.hoc.2009.04.005. PMID 19577167.
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  30. Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 226. ISBN 978-0781775960.
  31. Agarwal A, Pathak S, Gujral S (October 2006). "Sinus histiocytosis with massive lymphadenopathy--a review of seven cases". Indian J Pathol Microbiol 49 (4): 509–15. PMID 17183839.
  32. Bailey, D. 24 August 2010.
  33. Stedman's Medical Dictionary. 27th Ed.
  34. Viswanathan P, Raghunathan K, Majhi U, Pandit RV, Shanthi R, Rajkumar T (1997). Emperipolesis : an electron microscopic characteristic in RDD (Rosai-Dorfaman disease) : a case report. pp. 14-6. http://www.ijmpo.org/article.asp?issn=0971-5851;year=1997;volume=18;issue=1;spage=14;epage=16;aulast=Viswanathan;type=0.
  35. Lyons DJ, Gautam A, Clark J, et al. (January 1992). "Lymphocyte macrophage interactions: peripolesis of human alveolar macrophages". Eur. Respir. J. 5 (1): 59–66. PMID 1577151.
  36. 36.0 36.1 Taniguchi, I.; Murakami, G.; Sato, A.; Fujiwara, D.; Ichikawa, H.; Yajima, T.; Kohama, G. (Oct 2003). "Lymph node hyalinization in elderly Japanese.". Histol Histopathol 18 (4): 1169-80. PMID 12973685.