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.


==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===
==Lymph node hyalinization==
Features:<ref name=Ref_ILNP190>{{Ref ILNP|190}}</ref>
*[[AKA]] ''hyalinized lymph node''.
*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:
*[http://commons.wikimedia.org/wiki/File:Kimura_disease_-_very_high_mag.jpg Kimura disease - very high mag. (WC)].
*[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==
===General===
*Abbreviated ''LCH''.
*Genetic thingy.
*Looks like eosinophilic granuloma of the lung - see ''[[Medical_lung_diseases#Pulmonary_Langerhans_cell_histiocytosis|medical lung diseases]]''.
 
===Microscopic===
Features:
*Langerhans cells histiocytes:
**Clusters of cells (histiocytes) with a reniform (kidney-shaped) nucleus and abundant foamy cytoplasm.
**+/-Eosinophils - often prominent.


Images:
====Images====
*[http://commons.wikimedia.org/wiki/File:Langerhans_cell_histiocytosis_-_very_high_mag.jpg LCH - lymph node - very high mag. (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Langerhans_cell_histiocytosis_-_high_mag.jpg LCH - lymph node - high mag. (WC)].
Image: Hyalinized lymph node -- intermed mag.jpg | Hyalinized LN - intermed. mag.
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)].


===IHC===
===Sign out===
*CD1a +ve.
*Not reported.
*S100 +ve.


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