Difference between revisions of "Lymph node pathology"

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Haematologic malignancies (in lymph nodes) are dealt with in other articles - see ''[[haematopathology]]'' and ''[[lymphoma]]''.
Haematologic malignancies (in lymph nodes) are dealt with in other articles - see ''[[haematopathology]]'' and ''[[lymphoma]]''.
==Overview==
Clinical:
*Lymphadenopathy.
Differential diagnosis:<ref>URL: [http://path.upmc.edu/cases/case289.html http://path.upmc.edu/cases/case289.html]. Accessed on: 14 January 2012.</ref>
*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==
==Overview in a table==
{| class="wikitable"
{| class="wikitable sortable"
! Entity
! Entity
! Key feature
! Key feature
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| tingible body macrophages, normal dark/light GC pattern
| tingible body macrophages, normal dark/light GC pattern
| BCL2 -ve
| BCL2 -ve
| infection (Toxoplasmosis, [[HIV]]/AIDS), [[Hodgkin's lymphoma]]
| infection ([[Toxoplasmosis]], [[HIV]]/AIDS), [[Hodgkin's lymphoma]]
| image ?  
| image ?  
|-
|-
| Metastasis
| [[Lymph node metastasis]]
| foreign cell population, usu. in subcapsular sinuses   
| foreign cell population, usu. in subcapsular sinuses   
| +/-nuclear atypia, +/-malignant architecture
| +/-nuclear atypia, +/-malignant architecture
| dependent on tumour type (see ''[[IHC]]'')
| dependent on tumour type (see ''[[IHC]]'')
| dependent on morphology
| dependent on morphology, [[endometriosis]] (mimics adenocarcinoma), ectopic decidua (mimics [[SCC]])
| [http://commons.wikimedia.org/wiki/File:Crc_met_to_node1.jpg CRC met], [http://commons.wikimedia.org/wiki/File:Breast_carcinoma_in_a_lymph_node.jpg Breast met], [http://commons.wikimedia.org/wiki/File:Lymph_node_with_papillary_thyroid_carcinoma.jpg PTC met]
| [[Image:Crc_met_to_node1.jpg|thumb|center|125px| CRC metastasis]] [[Image:Breast_carcinoma_in_a_lymph_node.jpg|thumb|center|125px | Breast metastasis]]
|-
|-
| Progressive transformation of germinal centers
| [[Progressive transformation of germinal centers]]
| large (atypical) germinal centers
| large (atypical) germinal centers
| poorly demarcated germinal center (GC)/mantle zone interfaces, expanded mantle zone
| poorly demarcated germinal center (GC)/mantle zone interfaces, expanded mantle zone
| IHC to r/o ''nodular lymphocyte predominant [[Hodgkin lymphoma]]'' (NLPHL)
| IHC to r/o ''nodular lymphocyte predominant [[Hodgkin lymphoma]]'' (NLPHL)
| NLPHL, follicular hyperplasia
| NLPHL, follicular hyperplasia
| [http://commons.wikimedia.org/wiki/File:Progressive_transformation_of_germinal_centres_-1-_very_low_mag.jpg], [http://commons.wikimedia.org/wiki/File:Progressive_transformation_of_germinal_centres_-1-_low_mag.jpg]
| [[Image:Progressive transformation_of_germinal_centres_-1-_very_low_mag.jpg|thumb|center|150px | PTGC - very low mag.]]  
|-
|-
| Toxoplasmosis
| [[Toxoplasmosis]]
| large follicles; epithelioid cells perifollicular & intrafollicular
| large follicles; epithelioid cells perifollicular & intrafollicular
| reactive GCs, monocytoid cell clusters, epithelioid cells
| reactive GCs, monocytoid cell clusters, epithelioid cells
| IHC  for toxoplasma
| IHC  for toxoplasma
| NSRFH, HIV/AIDS, Hodgkin's lymphoma
| NSRFH, HIV/AIDS, [[Hodgkin's lymphoma]]
| [http://commons.wikimedia.org/wiki/File:Toxoplasmosis_lymphadenopathy_-_low_mag.jpg], [http://commons.wikimedia.org/wiki/File:Toxoplasmosis_lymphadenopathy_-b-_high_mag.jpg]
| [[Image:Toxoplasmosis_lymphadenopathy_-_low_mag.jpg|thumb|center|150px | TL - low mag.]]
|-
|-
| Kikuchi disease (histiocystic necrotizing lymphadenitis)
| [[Kikuchi disease]] (histiocystic necrotizing lymphadenitis)
| No PMNs
| No PMNs
| histiocytes, [[necrosis]]
| histiocytes, [[necrosis]]
| IHC for large cell lymphoma (CD30 + others)
| IHC for large cell lymphoma (CD30 + others)
| SLE (has (blue) hematoxylin bodies in necrotic areas), large cell lymphomas
| [[SLE]] (has (blue) hematoxylin bodies in necrotic areas), large cell lymphomas
| [http://commons.wikimedia.org/w/index.php?title=File:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg]
| [[Image:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg |thumb|center|150px| HNL - very high mag.]]
|-
|-
| Cat-scratch disease  
| [[Cat-scratch disease]]
| PMNs in necrotic area
| PMNs in necrotic area
| "stellate" (or serpentine) shaped microabscesses, granulomas  
| "stellate" (or serpentine) shaped microabscesses, granulomas  
| B. henselae, [[Dieterle stain]]
| B. henselae, [[Dieterle stain]]
| [[HIV]]/AIDS, NSRFH
| [[HIV]]/AIDS, NSRFH
| [http://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-_very_low_mag.jpg]
| [[Image:Cat_scratch_disease_-_very_low_mag.jpg|thumb|center|150px|Cat scratch - very low mag.]]
|-
|-
| Dermatopathic lymphadenopathy  
| [[Dermatopathic lymphadenopathy]]
| melanin-laden histiocytes
| melanin-laden histiocytes
| histiocytosis
| [[histiocytosis]]
| S100+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells)
| [[S-100]]+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells)
| DDx ?
| [[cutaneous T-cell lymphoma]]
| [http://commons.wikimedia.org/wiki/File:Dermatopathic_lymphadenopathy_-_low_mag.jpg], [http://commons.wikimedia.org/wiki/File:Dermatopathic_lymphadenopathy_-_intermed_mag.jpg]  
| [[Image:Dermatopathic_lymphadenopathy_-_intermed_mag.jpg |thumb|center|150px| DL - intermed. mag.]]  
|-
|-
| Kimura disease
| [[Kimura disease]]
| eosinophils
| eosinophils
| angiolymphoid proliferation (thick-walled blood vessels with hobnail endothelial cells)
| angiolymphoid proliferation (thick-walled blood vessels with [[hobnail]] endothelial cells)
| IHC ?
| IHC ?
| eosinophilic granuloma
| [[Langerhans cell histiocytosis]], drug reaction, [[angiolymphoid hyperplasia with eosinophilia]]
| [http://commons.wikimedia.org/wiki/File:Kimura_disease_-_very_high_mag.jpg]
| [[Image:Kimura_disease_-_very_high_mag.jpg|thumb|center|150px|Kimura disease - very high mag.]]
|-
|-
| Langerhans cell histiocytosis  
| [[Langerhans cell histiocytosis]]
| abundant histiocytes with reniform nuclei
| abundant histiocytes with reniform nuclei
| often prominent eosinophilia
| often prominent eosinophilia
| S100+, CD1a+
| [[S-100]]+, CD1a+
| Kimura disease (eosinophilia), Rosai-Dorfman disease
| [[Kimura disease]] (eosinophilia), [[Rosai-Dorfman disease]]
| [http://commons.wikimedia.org/w/index.php?title=File:Langerhans_cell_histiocytosis_-_very_high_mag.jpg]
| [[Image:Langerhans_cell_histiocytosis_-_very_high_mag.jpg|thumb|center|150px|LCH - very high mag.]]
|-
|-
| Rosai-Dorfman disease
| [[Rosai-Dorfman disease]]
| sinus histiocytosis
| sinus histiocytosis
| emperipolesis (intact cell within a macrophage)
| emperipolesis (intact cell within a macrophage)
| S100+, CD1a-
| [[S-100]]+, CD1a-
| Langerhans cell histiocytosis
| Langerhans cell histiocytosis
| [http://commons.wikimedia.org/w/index.php?title=File:Emperipolesis_-_very_high_mag.jpg]  
| [[Image:Emperipolesis_-_very_high_mag.jpg |thumb|center|150px | RDD - very high mag.]]  
|-
|-
| Systemic lupus erythematosus lymphadenopathy  
| [[Systemic lupus erythematosus]] lymphadenopathy  
| (blue) hematoxylin bodies
| (blue) hematoxylin bodies
| necrosis, no PMNs
| necrosis, no PMNs
| IHC for large cell lymphoma (CD30 + others)
| IHC for large cell lymphoma (CD30 + others)
| Kikuchi disease, large cell lymphomas
| [[Kikuchi disease]], large cell [[lymphoma]]s
| [http://commons.wikimedia.org/wiki/File:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg]
| [[Image:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg|thumb|center|150px | SLEL - high mag.]]
|-
|-
| Castleman disease, hyaline vascular variant
| [[Castleman disease]], hyaline vascular variant
| thick mantle cell layer with laminar appearance ("onion skin" layering)
| thick mantle cell layer with laminar appearance ("onion skin" layering)
| hyaline (pink crap), lollipops (large vessels into GC), no mitoses in GC
| hyaline (pink crap), lollipops (large vessels into GC), no mitoses in GC
| IHC - to r/o [[mantle cell lymphoma]]
| IHC - to r/o [[mantle cell lymphoma]]
| mantle cell lymphoma, [[HIV]]/AIDS
| mantle cell lymphoma, [[HIV]]/AIDS
| [http://commons.wikimedia.org/wiki/File:Castleman_disease_-_intermed_mag.jpg], [http://commons.wikimedia.org/wiki/File:Castleman_disease_-_high_mag.jpg]
| [[Image:Castleman_disease_-_intermed_mag.jpg|thumb|center|150px | CD - intermed. mag.]]
|-
|-
| Castleman disease, plasma cell variant
| Castleman disease, plasma cell variant
| thick mantle cell layer
| thick mantle cell layer
| sinus perserved, interfollicular plasma cells, mitoses in GC
| sinus perserved, interfollicular plasma cells, mitoses in GC
| HHV-8
| [[HHV-8]]
| HIV/AIDS
| HIV/AIDS
| image ?
| image ?
|-
| [[Intranodal palisaded myofibroblastoma]]
| spindle cells with nuclear palisading
| [[RBC extravasation]], fibrillary bodies with a central vessel "amianthoid fibers"
| SMA+, cyclin D1+
| [[schwannoma]]
| [[Image:Intranodal_palisaded_myofibroblastoma_-_very_high_mag.jpg|thumb|center|150px|IPM - very high mag.]]
|-
<!-- | entity  
<!-- | entity  
| key feature
| key feature
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|}
|}


==Metastasis==
==Lymph node metastasis==
===General===
{{Main|Lymph node metastasis}}
*Determination of ''lymph node status'' is probably the most common indication 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.


===Microscopic===
==Kaposi sarcoma==
Features:
{{Main|Kaposi sarcoma}}
*Foreign cell population - '''key feature'''.
*One of the few non-lymphoid primary lymph node tumours.<ref name=pmid1918406>{{Cite journal  | last1 = Bigotti | first1 = G. | last2 = Coli | first2 = A. | last3 = Mottolese | first3 = M. | last4 = Di Filippo | first4 = F. | title = Selective location of palisaded myofibroblastoma with amianthoid fibres. | journal = J Clin Pathol | volume = 44 | issue = 9 | pages = 761-4 | month = Sep | year = 1991 | doi =  | PMID = 1918406 | PMC = 496726 }}</ref>
**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:
*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.


Images:
==Melanocytic nevi==
*[http://commons.wikimedia.org/wiki/File:Breast_carcinoma_in_a_lymph_node.jpg Breast carcinoma LN metastasis (WC)].
{{Main|Melanocytic lesions}}
*[http://commons.wikimedia.org/wiki/File:Lymph_node_with_papillary_thyroid_carcinoma.jpg Thyroid carcinoma LN metastasis (WC)].
:See: ''[[Dermatopathic lymphadenopathy]]''.
*[http://commons.wikimedia.org/wiki/File:Crc_met_to_node1.jpg Colorectal carcinoma LN metastasis (WC)].
*Benign melanocytic nevi can be found in lymph nodes.<ref name=pmid1918406>{{Cite journal  | last1 = Bigotti | first1 = G. | last2 = Coli | first2 = A. | last3 = Mottolese | first3 = M. | last4 = Di Filippo | first4 = F. | title = Selective location of palisaded myofibroblastoma with amianthoid fibres. | journal = J Clin Pathol | volume = 44 | issue = 9 | pages = 761-4 | month = Sep | year = 1991 | doi =  | PMID = 1918406 | PMC = 496726 }}</ref>


==Progressive transformation of germinal centers==
==Progressive transformation of germinal centers==
{{Main|Progressive transformation of germinal centers}}
*Abbreviated as ''PTGC''.
*Abbreviated as ''PTGC''.
===General===
*Benign.
*Classically in younger patients.
*Associated with nodular lymphocyte predominant [[Hodgkin's lymphoma]] (NLPHL); NLPHL found in up to 5% in a 7 year follow-up.<ref name=pmid12145465>{{cite journal |author=Verma A, Stock W, Norohna S, Shah R, Bradlow B, Platanias LC |title=Progressive transformation of germinal centers. Report of 2 cases and review of the literature |journal=Acta Haematol. |volume=108 |issue=1 |pages=33–8 |year=2002 |pmid=12145465 |doi= |url=}}</ref>
Clinical:
*Asymptomatic lymphadenopathy.
===Microscopic===
Features:
*Follicular hyperplasia (many follicles).
*'''Focally''' large germinal centers with:
**Poorly demarcated germinal center (GC)/mantle zone interfaces (as GCs infiltrated by mantle zone lymphocytes) -- '''key feature'''.<ref name=pmid12145465/>
**Expanded mantle zone.
Images:
*[http://commons.wikimedia.org/wiki/File:Progressive_transformation_of_germinal_centres_-1-_very_low_mag.jpg PTGCs - very low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Progressive_transformation_of_germinal_centres_-1-_low_mag.jpg PTGCs - low mag. (WC)].


==Reactive follicular hyperplasia==
==Reactive follicular hyperplasia==
===General===
{{Main|Reactive follicular hyperplasia}}
*Many causes - including: bacteria, viruses, chemicals, drugs, allergens.
**In only approximately 10% can definitive cause be identified.<ref name=Ref_ILNP174>{{Ref_ILNP|174}}</ref>
 
===Microscopic===
Features:<ref name=Ref_ILNP179>{{Ref_ILNP|179}}</ref>
*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.
 
IHC:
*BCL2 -ve.
 
Image: [http://pleiad.umdnj.edu/hemepath/normal_node/normal_node.html Normal lymph node (umdnj.edu)].


==Diffuse paracortical hyperplasia==
==Diffuse paracortical hyperplasia==
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==Sinus histiocytosis==
==Sinus histiocytosis==
===General===
:Should '''not''' be confused with ''[[sinus histiocytosis with massive lymphadenopathy]]'', also known as Rosai-Dorfman disease.
*Benign.
{{Main|Sinus histiocytosis}}
 
===Microscopic===
Features:<ref name=Ref_ILNP179>{{Ref_ILNP|179}}</ref>
*Sinuses distended with histiocytes - '''key feature'''.
*Plasma cells increased.
 
Notes:
*Sinus histiocytosis should prompt consideration of Rosai-Dorfman disease.
**Look for large nuclei (~2x lymphocyte) with prominent nucleoli.


==Kikuchi disease==
==Kikuchi disease==
===General===
*[[AKA]] ''histiocytic necrotising lymphadenitis'' (HNL).<ref name="pmid15570824">{{cite journal |author=Kaushik V, Malik TH, Bishop PW, Jones PH |title=Histiocytic necrotising lymphadenitis (Kikuchi's disease): a rare cause of cervical lymphadenopathy |journal=Surgeon |volume=2 |issue=3 |pages=179–82 |year=2004 |month=June |pmid=15570824 |doi= |url=}}</ref>
*AKA ''histiocytic necrotising lymphadenitis'' (HNL),<ref name="pmid15570824">{{cite journal |author=Kaushik V, Malik TH, Bishop PW, Jones PH |title=Histiocytic necrotising lymphadenitis (Kikuchi's disease): a rare cause of cervical lymphadenopathy |journal=Surgeon |volume=2 |issue=3 |pages=179–82 |year=2004 |month=June |pmid=15570824 |doi= |url=}}</ref> and ''Kikuchi-Fujimoto disease''.
*[[AKA]] ''Kikuchi-Fujimoto disease''.
*Rare disease that may mimic cancer, esp. lymphoma.
{{Main|Kikuchi disease}}
**May cause fever & systemic symptoms.<ref name=pmid20121621>{{cite journal |author=Hutchinson CB, Wang E |title=Kikuchi-Fujimoto disease |journal=Arch. Pathol. Lab. Med. |volume=134 |issue=2 |pages=289–93 |year=2010 |month=February |pmid=20121621 |doi= |url=}}</ref>
 
Epidemiology:<ref name=pmid20121621/>
*Usually <40 years old.
*Asian.
*Female:Male = 3:1.<ref>URL: [http://emedicine.medscape.com/article/210752-overview http://emedicine.medscape.com/article/210752-overview]. Accessed on: 3 June 2010.</ref>
 
Treatment:
*Usually self-limited.<ref name=pmid20121621/>
*Oral corticosteroids.
 
DDx:
*Non-Hodgkin lymphoma.
*Systemic lupus erythematosus.
**Hematoxyphil bodies in necrotic foci.
***Dark blue irregular bodies on H&E.
 
===Micrograph===
Features (the three main features - just as the name suggests):<ref>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 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.</ref>
*Histiocytes.
**May be crescentic.
*Necrosis (due to apoptosis) - paracortical areas.<ref name=pmid20121621/>
**Necrosis without neutrophils - '''key feature'''.
*Lymphocytes (CD8 +ve).
*Plasmacytoid dendritic cells.
 
Notes:
*Dendritic cell - vaguely resembles a macrophage:<ref>URL: [http://www.healthsystem.virginia.edu/internet/hematology/hessedd/benignhematologicdisorders/normal-hematopoietic-cells/dendritic-cell.cfm?drid=214 http://www.healthsystem.virginia.edu/internet/hematology/hessedd/benignhematologicdisorders/normal-hematopoietic-cells/dendritic-cell.cfm?drid=214]. Accessed on: 3 June 2010.</ref>
**Long membrane projections - '''key feature'''.
**Abundant blue-grey cytoplasm, +/- ground-glass appearance.
**Nucleus: small, ovoid, usu. single nucleolus.
 
Images:
*[http://commons.wikimedia.org/w/index.php?title=File:Histiocytic_necrotizing_lymphadenitis_-_intermed_mag.jpg Kikuchi disease - intermed mag (WC)].
*[http://commons.wikimedia.org/w/index.php?title=File:Histiocytic_necrotizing_lymphadenitis_-_high_mag.jpg Kikuchi disease - high mag (WC)].
*[http://commons.wikimedia.org/w/index.php?title=File:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg Kikuchi disease - very high mag (WC)].
 
===IHC===
*CD68 +ve.
*CD8 +ve - usu. predominant.
*CD4, CD20, CD3, and CD30 - mixed.  
**Done to excluded lymphoma; esp. large cell lymphomas;<ref name=pmid19577167>{{cite journal |author=Good DJ, Gascoyne RD |title=Atypical lymphoid hyperplasia mimicking lymphoma |journal=Hematol. Oncol. Clin. North Am. |volume=23 |issue=4 |pages=729–45 |year=2009 |month=August |pmid=19577167 |doi=10.1016/j.hoc.2009.04.005 |url=}}</ref> should show a mixed population of lymphocytes.
*Others:
**CD56 -ve.


==Systemic lupus erythematosus lymphadenopathy==
==Systemic lupus erythematosus lymphadenopathy==
===General===
{{Main|Systemic lupus erythematosus lymphadenopathy}}
*Lymphadenopathy associated with systemic lupus erythematosus (SLE).
 
===Microscopic===
Features:<ref name=pmid9406250>{{Cite journal  | last1 = Kojima | first1 = M. | last2 = Nakamura | first2 = S. | last3 = Itoh | first3 = H. | last4 = Yoshida | first4 = K. | last5 = Asano | first5 = S. | last6 = Yamane | first6 = N. | last7 = Komatsumoto | first7 = S. | last8 = Ban | first8 = S. | last9 = Joshita | first9 = T. | title = Systemic lupus erythematosus (SLE) lymphadenopathy presenting with histopathologic features of Castleman' disease: a clinicopathologic study of five cases. | journal = Pathol Res Pract | volume = 193 | issue = 8 | pages = 565-71 | month =  | year = 1997 | doi =  | PMID = 9406250 }}</ref>
*Necrosis.
*Hematoxylin bodies (in necrotic foci).
**Dark blue irregular bodies on H&E.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg SLE lymphadenopathy - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Systemic_lupus_erythematosus_lymphadenopathy_-_very_high_mag.jpg SLE lymphadenopathy - very high mag. (WC)].
 
DDx:
*Kikuchi disease.


==Castleman disease==
==Castleman disease==
===General===
*[[AKA]] ''angiofollicular lymph node hyperplasia'', ''giant lymph node hyperplasia''.<ref>URL: [http://www.mayoclinic.com/health/castleman-disease/DS01000 http://www.mayoclinic.com/health/castleman-disease/DS01000]. Accessed on: 17 June 2010.</ref>
*[[AKA]] ''angiofollicular lymph node hyperplasia'', ''giant lymph node hyperplasia''.<ref>URL: [http://www.mayoclinic.com/health/castleman-disease/DS01000 http://www.mayoclinic.com/health/castleman-disease/DS01000]. Accessed on: 17 June 2010.</ref>
*Benign.
*Abbreviated '''CD'''.
*Abbreviated '''CD'''.
 
{{Main|Castleman disease}}
===Classification===
CD is grouped by histologic appearance:<ref name=Ref_ILNP228>{{Ref ILNP|228}}</ref>
#Hyaline vascular (HV) variant (described by Castleman).
#*Usually unicentric.
#*Typically mediastinal or axial.
#*More common than plasma cell variant; represents 80-90% of CD cases.
#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.<ref name=pmid19546611>{{Cite journal  | last1 = Cronin | first1 = DM. | last2 = Warnke | first2 = RA. | title = Castleman disease: an update on classification and the spectrum of associated lesions. | journal = Adv Anat Pathol | volume = 16 | issue = 4 | pages = 236-46 | month = Jul | year = 2009 | doi = 10.1097/PAP.0b013e3181a9d4d3 | PMID = 19546611 }}</ref>
 
===Microscopic===
====Hyaline-vascular variant (HVV)====
Features:<ref>URL: [http://www.ispub.com/journal/the_internet_journal_of_otorhinolaryngology/volume_9_number_2_11/article/a_rare_case_of_castleman_s_disease_presenting_as_cervical_neck_mass.html http://www.ispub.com/journal/the_internet_journal_of_otorhinolaryngology/volume_9_number_2_11/article/a_rare_case_of_castleman_s_disease_presenting_as_cervical_neck_mass.html]. Accessed on: 15 June 2010.</ref><ref name=Ref_ILNP236>{{Ref ILNP|236}}</ref>
*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:
*[http://commons.wikimedia.org/wiki/File:Castleman_disease_-_high_mag.jpg CD HVV - "lollipop" sign - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Castleman_disease_-_intermed_mag.jpg CD HVV - showing expanded mantle zone - intermed. mag. (WC)].
 
====Plasma cell variant====
Features:<ref name=Ref_ILNP236>{{Ref ILNP|236}}</ref>
*Interfollicular sheets of plasma cells - '''key feature'''.
*Active germinal centers - mitoses present.
*Sinus perserved.
 
===IHC===
Hyaline-vascular variant:
*Stains to exclude [[mantle cell lymphoma]]:
**Cyclin D1.
 
Plasma cell variant:
*HHV-8 +ve.


==Cat-scratch disease==
==Cat-scratch disease==
===General===
*[[AKA]] ''cat scratch fever''.
*[[AKA]] ''Cat-scratch fever''.
{{Main|Cat scratch disease}}
*Infection caused ''Bartonella henselae'',<ref name=pmid19332922>{{Cite journal  | last1 = Jerris | first1 = RC. | last2 = Regnery | first2 = RL. | title = Will the real agent of cat-scratch disease please stand up? | journal = Annu Rev Microbiol | volume = 50 | issue =  | pages = 707-25 | month =  | year = 1996 | doi = 10.1146/annurev.micro.50.1.707 | PMID = 8905096 }}</ref> a gram-negative bacilla (0.3-1.0 x 0.6-3.0 micrometers) in chains, clumps, or singular.<ref name=Ref_ILNP110>{{Ref ILNP|110}}</ref>
*Treatment: antibiotics.
 
===Clinical===
Features:<ref name=Ref_ILNP113>{{Ref ILNP|113}}</ref>
*Usually unilateral.
**May be disseminated in individuals with immune dysfunction.
*Contact with cats.
 
===Micrograph===
Features:<ref name=Ref_ILNP113>{{Ref ILNP|113}}</ref>
*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.
 
Stains:
*Warthin-Starry stain +ve.
*B. henselae IHC stain +ve.
 
Images:
*[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://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-_very_low_mag.jpg CSD - very low mag. - showing serpentine shaped microabscesses (WC)].
*[http://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-b-_high_mag.jpg CSD - high mag. - showing neutrophilic abscesses (WC)].


==Toxoplasma lymphadenitis==
==Toxoplasma lymphadenitis==
{{Main|Toxoplasma}}
===General===
===General===
*Caused by protozoan ''Toxoplasma gondii''.
*Caused by protozoan ''Toxoplasma gondii''.
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==Dermatopathic lymphadenopathy==
==Dermatopathic lymphadenopathy==
===General===
{{Main|Dermatopathic lymphadenopathy}}
*Lymphadenopathy associated with a skin lesion - '''key feature'''.
*May be benign or malignant (e.g. T-cell lymphoma).
 
===Microscopic===
Features:<ref name=ILNP226>{{Ref ILNP|226}}</ref>
*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.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Dermatopathic_lymphadenopathy_-_low_mag.jpg DL - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Dermatopathic_lymphadenopathy_-_intermed_mag.jpg DL - intermed. mag. (WC)].
 
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.
 
IHC:
*Interdigitating dendritic cells: S100 +ve, CD1a -ve.
*Langerhans cells: S100 +ve, CD1a +ve.


==Kimura lymphadenopathy==
==Kimura lymphadenopathy==
===General===
{{Main|Kimura disease}}
*[[AKA]] ''eosinophilic lymphogranuloma'', ''Kimura disease''.
*Chronic inflammatory disorder - suspected to be infectious.


Clinical:
==Rosai-Dorfman disease==
*Usually neck, periauricular.
*Abbreviated ''RDD''.
*Peripheral blood eosinophilia.
*[[AKA]] ''sinus histiocytosis with massive lymphadenopathy'', abbreviated ''SHML''.
*Increased blood IgE.
{{Main|Rosai-Dorfman disease}}


===Epidemiology===
==Langerhans cell histiocytosis==
*Males > females.
{{Main|Langerhans cell histiocytosis}}
*Young.
*Asian.
 
===Microscopic===
Features:<ref name=Ref_ILNP190>{{Ref ILNP|190}}</ref>
*Angiolymphoid proliferation.
**Thick walled blood vessels with (plump) hobnail endothelial cells.<ref>URL: [http://emedicine.medscape.com/article/1098777-diagnosis http://emedicine.medscape.com/article/1098777-diagnosis]. Accessed on: 8 August 2010.</ref>
*Eosinophils - abundant - '''key feature'''.
 
Notes:
*Abundant eosinophils: consider Langerhans cell histiocytosis.


Images:
==Lymph node hyalinization==
*[http://commons.wikimedia.org/wiki/File:Kimura_disease_-_very_high_mag.jpg Kimura disease - very high mag. (WC)].
*[[AKA]] ''hyalinized lymph node''.
*[http://commons.wikimedia.org/wiki/File:Kimura_disease_-_high_mag.jpg Kimura disease - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Kimura_disease_-_intermed_mag.jpg Kimura disease - intermed. mag. (WC)].
 
===IHC===
*Used to rule-out a clonal population.
 
==Rosai-Dorfman disease==
===General===
===General===
*[[AKA]] ''sinus histiocytosis with massive lymphadenopathy'', abbreviated ''SHML''.<ref name=pmid17183839>{{cite journal |author=Agarwal A, Pathak S, Gujral S |title=Sinus histiocytosis with massive lymphadenopathy--a review of seven cases |journal=Indian J Pathol Microbiol |volume=49 |issue=4 |pages=509–15 |year=2006 |month=October |pmid=17183839 |doi= |url=}}</ref>
*Benign.
*Super rare.
*Associated with aging.<ref name=pmid12973685>{{Cite journal | last1 = Taniguchi | first1 = I. | last2 = Murakami | first2 = G. | last3 = Sato | first3 = A. | last4 = Fujiwara | first4 = D. | last5 = Ichikawa | first5 = H. | last6 = Yajima | first6 = T. | last7 = Kohama | first7 = G. | title = Lymph node hyalinization in elderly Japanese. | journal = Histol Histopathol | volume = 18 | issue = 4 | pages = 1169-80 | month = Oct | year = 2003 | doi = | PMID = 12973685 }}</ref>
*Prognosis - good.


===Microscopic===
===Microscopic===
Features:
Features:
*Sinus histiocytosis:
*Hyaline material (acellular pink stuff on H&E) within a [[lymph node]].
**Histiocytes - abundant.
***Singular large round nuclei<ref>DB. 24 August 2010.</ref> ~2x the size of resting lymphocyte.
****Prominent nucleolus - visible with 10x objective.
***Abundant cytoplasm.
*Emperipolesis (from ''Greek'': ''em'' = inside, ''peri'' = around, ''polemai'' = wander about<ref>Stedman's Medical Dictionary. 27th Ed.</ref>):
**Histiocytes contain other whole cells: neutrophils, lymphocytes, plasma cells.
***The "eaten" cell is within a vacuole;<ref>{{cite journal |author=Viswanathan P, Raghunathan K, Majhi U, Pandit RV, Shanthi R, Rajkumar T|title=Emperipolesis : an electron microscopic characteristic in RDD (Rosai-Dorfaman disease) : a case report |volume= |issue=1|pages=14-6 |year=1997 |month= |pmid= |doi= |url=http://www.ijmpo.org/article.asp?issn=0971-5851;year=1997;volume=18;issue=1;spage=14;epage=16;aulast=Viswanathan;type=0}}</ref> thus, it should have a clear halo around it.
***Thought to be related to ''peripolesis''; the attachment of a cell to another.<ref name=pmid1577151>{{cite journal |author=Lyons DJ, Gautam A, Clark J, ''et al.'' |title=Lymphocyte macrophage interactions: peripolesis of human alveolar macrophages |journal=Eur. Respir. J. |volume=5 |issue=1 |pages=59–66 |year=1992 |month=January |pmid=1577151 |doi= |url=}}</ref>


Images:
Subdivided into:<ref name=pmid12973685/>
*[http://commons.wikimedia.org/wiki/File:Emperipolesis_-_very_high_mag.jpg Emperipolesis in SHML (WC)].
*Mediastinal-type.
*[http://commons.wikimedia.org/wiki/File:Rosai-Dorfman_disease_-_very_high_mag.jpg Rosai-Dorfman disease (WC)].
**Usually in medullary sinus.
*[http://commons.wikimedia.org/wiki/File:Rosai-dorfman.jpg Rosai-Dorfman disease - S100 showing emperipolesis (WC)].
**Onion peel-like appearance.
*Pelvic-type hyalinization.
**Discrete round, eosinophilic, glassy appearance at low power, whirled/fibrous at high power.
**+/-Calcification.  


DDx:
DDx:
*Other histiocytosis:
*[[Amyloidosis]] - cotton candy-like appearance, usu. no calcifications.
**Langerhans cell histiocytosis.
**Erdheim-Chester disease.
*Infection, e.g. Rhinoscleroma (nasopharynx), xanthomatous pyelonephritis.
*Xanthomatous change.
 
===IHC===
*CD68 +ve.
*S100 +ve.
**Useful for seeing emperipolesis.
*CD1a -ve.
**CD1a positive in Langerhans cell histiocytosis.
 
==Langerhans cell histiocytosis==
{{Main|Langerhans cell histiocytosis}}


===Microscopic===
====Images====
Features:
<gallery>
*Langerhans cells histiocytes - '''key feature'''.
Image: Hyalinized lymph node -- intermed mag.jpg | Hyalinized LN - intermed. mag.
**Clusters of cells (histiocytes) with a reniform (kidney-shaped) nucleus and abundant foamy cytoplasm.
Image: Hyalinized lymph node - alt -- intermed mag.jpg | Hyalinized LN - intermed. mag.
Image: Hyalinized lymph node -- high mag.jpg | Hyalinized LN - high mag.
Image: Hyalinized lymph node -- very high mag.jpg | Hyalinized LN - very high mag.
</gallery>
www:
*[http://www.flickriver.com/photos/euthman/sets/72157594513987154/ Lymph node with amyloidosis - several images (flickriver.com)].


See ''[[Langerhans cell histiocytosis]]'' for details.
===Sign out===
*Not reported.


==See also==
==See also==
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[[Category:Haematopathology]]
[[Category:Haematopathology]]
[[Category:Lymph node pathology|Lymph node pathology]]

Latest revision as of 15:16, 16 February 2021

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)
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
PTGC - very low mag.
Toxoplasmosis large follicles; epithelioid cells perifollicular & intrafollicular reactive GCs, monocytoid cell clusters, epithelioid cells IHC for toxoplasma NSRFH, HIV/AIDS, Hodgkin's lymphoma
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
Cat scratch - very low mag.
Dermatopathic lymphadenopathy melanin-laden histiocytes histiocytosis S-100+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells) cutaneous T-cell lymphoma
DL - intermed. mag.
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 S-100+, CD1a+ Kimura disease (eosinophilia), Rosai-Dorfman disease
LCH - very high mag.
Rosai-Dorfman disease sinus histiocytosis emperipolesis (intact cell within a macrophage) S-100+, CD1a- Langerhans cell histiocytosis
RDD - very high mag.
Systemic lupus erythematosus lymphadenopathy (blue) hematoxylin bodies necrosis, no PMNs IHC for large cell lymphoma (CD30 + others) Kikuchi disease, large cell lymphomas
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
CD - intermed. mag.
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

Main article: Lymph node metastasis

Kaposi sarcoma

Main article: Kaposi sarcoma
  • One of the few non-lymphoid primary lymph node tumours.[3]

Melanocytic nevi

Main article: Melanocytic lesions
See: Dermatopathic lymphadenopathy.
  • Benign melanocytic nevi can be found in lymph nodes.[3]

Progressive transformation of germinal centers

Main article: Progressive transformation of germinal centers
  • Abbreviated as PTGC.

Reactive follicular hyperplasia

Main article: Reactive follicular hyperplasia

Diffuse paracortical hyperplasia

General

  • Benign.

Microscopic

Features:[4]

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

Sinus histiocytosis

Should not be confused with sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease.
Main article: Sinus histiocytosis

Kikuchi disease

  • AKA histiocytic necrotising lymphadenitis (HNL).[5]
  • AKA Kikuchi-Fujimoto disease.
Main article: Kikuchi disease

Systemic lupus erythematosus lymphadenopathy

Main article: Systemic lupus erythematosus lymphadenopathy

Castleman disease

  • AKA angiofollicular lymph node hyperplasia, giant lymph node hyperplasia.[6]
  • Abbreviated CD.
Main article: Castleman disease

Cat-scratch disease

  • AKA cat scratch fever.
Main article: Cat scratch disease

Toxoplasma lymphadenitis

Main article: Toxoplasma

General

  • Caused by protozoan Toxoplasma gondii.

Microscopic

Features:[7]

  • 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

Main article: Dermatopathic lymphadenopathy

Kimura lymphadenopathy

Main article: Kimura disease

Rosai-Dorfman disease

  • Abbreviated RDD.
  • AKA sinus histiocytosis with massive lymphadenopathy, abbreviated SHML.
Main article: Rosai-Dorfman disease

Langerhans cell histiocytosis

Main article: Langerhans cell histiocytosis

Lymph node hyalinization

  • AKA hyalinized lymph node.

General

  • Benign.
  • Associated with aging.[8]

Microscopic

Features:

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

Subdivided into:[8]

  • 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

  • Hyalinized LN - intermed. mag.

  • Hyalinized LN - intermed. mag.

  • Hyalinized LN - high mag.

  • Hyalinized LN - very high mag.

www:

Sign out

  • Not reported.

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 Bigotti, G.; Coli, A.; Mottolese, M.; Di Filippo, F. (Sep 1991). "Selective location of palisaded myofibroblastoma with amianthoid fibres.". J Clin Pathol 44 (9): 761-4. PMC 496726. PMID 1918406. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC496726/.
  4. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 179. ISBN 978-0781775960.
  5. ↑ Kaushik V, Malik TH, Bishop PW, Jones PH (June 2004). "Histiocytic necrotising lymphadenitis (Kikuchi's disease): a rare cause of cervical lymphadenopathy". Surgeon 2 (3): 179–82. PMID 15570824.
  6. ↑ URL: http://www.mayoclinic.com/health/castleman-disease/DS01000. Accessed on: 17 June 2010.
  7. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 113. ISBN 978-0781775960.
  8. ↑ 8.0 8.1 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.
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