Difference between revisions of "Lymph node pathology"

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*Neoplastic - lymphoma, carcinoma.
*Neoplastic - lymphoma, carcinoma.
*Endocrine - [[hyperthyroidism]].
*Endocrine - [[hyperthyroidism]].
*Trauma.
*Trauma.  
*Autoimmune - [[SLE]], [[RA]], [[dermatomyositis]].
*Autoimmune - [[SLE]], [[RA]], [[dermatomyositis]].
*Inflammatory - drugs (phenytoin).
*Inflammatory - drugs (phenytoin).
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| dependent on tumour type (see ''[[IHC]]'')
| dependent on tumour type (see ''[[IHC]]'')
| dependent on morphology, [[endometriosis]] (mimics adenocarcinoma), ectopic decidua (mimics [[SCC]])
| 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]]
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| 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]]
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| 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)
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| 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]]  
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| 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)
| [[cutaneous T-cell lymphoma]]
| [[cutaneous T-cell lymphoma]]
| [http://commons.wikimedia.org/wiki/File:Dermatopathic_lymphadenopathy_-_low_mag.jpg low mag. (WC)], [http://commons.wikimedia.org/wiki/File:Dermatopathic_lymphadenopathy_-_intermed_mag.jpg intermed. mag. (WC)]  
| [[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 ?
| [[Langerhans cell histiocytosis]], drug reaction, [[angiolymphoid hyperplasia with eosinophilia]]
| [[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 (WC)]  
| [[Image:Emperipolesis_-_very_high_mag.jpg |thumb|center|150px | RDD - very high mag.]]  
|-
|-
| [[Systemic lupus erythematosus]] lymphadenopathy  
| [[Systemic lupus erythematosus]] lymphadenopathy  
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| IHC for large cell lymphoma (CD30 + others)
| IHC for large cell lymphoma (CD30 + others)
| [[Kikuchi disease]], large cell [[lymphoma]]s
| [[Kikuchi disease]], large cell [[lymphoma]]s
| [http://commons.wikimedia.org/wiki/File:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg (WC)]
| [[Image:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg|thumb|center|150px | SLEL - high mag.]]
|-
|-
| [[Castleman disease]], hyaline vascular variant
| [[Castleman disease]], hyaline vascular variant
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| 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 intermed. mag. (WC)], [http://commons.wikimedia.org/wiki/File:Castleman_disease_-_high_mag.jpg high mag. (WC)]
| [[Image:Castleman_disease_-_intermed_mag.jpg|thumb|center|150px | CD - intermed. mag.]]
|-
|-
| Castleman disease, plasma cell variant
| Castleman disease, plasma cell variant
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| SMA+, cyclin D1+
| SMA+, cyclin D1+
| [[schwannoma]]
| [[schwannoma]]
| [http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=20080802163636511 (surgicalpathologyatlas.com)]
| [[Image:Intranodal_palisaded_myofibroblastoma_-_very_high_mag.jpg|thumb|center|150px|IPM - very high mag.]]
|-
|-
<!-- | entity  
<!-- | entity  
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==Lymph node metastasis==
==Lymph node metastasis==
===General===
{{Main|Lymph node metastasis}}
*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.<ref name=pmid18337039>{{Cite journal  | last1 = Mack | first1 = MG. | last2 = Rieger | first2 = J. | last3 = Baghi | first3 = M. | last4 = Bisdas | first4 = S. | last5 = Vogl | first5 = TJ. | title = Cervical lymph nodes. | journal = Eur J Radiol | volume = 66 | issue = 3 | pages = 493-500 | month = Jun | year = 2008 | doi = 10.1016/j.ejrad.2008.01.019 | PMID = 18337039 }}</ref>
**Shape - round more suspicious than oval.
*Sectioned:
**White firm lesion with irregular border - classic appearance.
**Non-fatty hilum.<ref name=pmid18337039/>
 
===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:
#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.
#Mimics of metastatic disease:
#*[[Endometriosis]].
#*Ectopic [[decidua]].<ref name=pmid15859655>{{Cite journal  | last1 = Wu | first1 = DC. | last2 = Hirschowitz | first2 = S. | last3 = Natarajan | first3 = S. | title = Ectopic decidua of pelvic lymph nodes: a potential diagnostic pitfall. | journal = Arch Pathol Lab Med | volume = 129 | issue = 5 | pages = e117-20 | month = May | year = 2005 | doi = 10.1043/1543-2165(2005)129e117:EDOPLN2.0.CO;2 | PMID = 15859655 }}</ref>
#*[[Endosalpingiosis]].<ref name=pmid20631604>{{Cite journal  | last1 = Corben | first1 = AD. | last2 = Nehhozina | first2 = T. | last3 = Garg | first3 = K. | last4 = Vallejo | first4 = CE. | last5 = Brogi | first5 = E. | title = Endosalpingiosis in axillary lymph nodes: a possible pitfall in the staging of patients with breast carcinoma. | journal = Am J Surg Pathol | volume = 34 | issue = 8 | pages = 1211-6 | month = Aug | year = 2010 | doi = 10.1097/PAS.0b013e3181e5e03e | PMID = 20631604 }}</ref>
#[[Soft_tissue_lesions#Lymph_node_metastases_in_sarcomas|Lymph node metastases in sarcomas]] are uncommon; they are seen in <3% of cases.<ref name=pmid8424704>{{Cite journal  | last1 = Fong | first1 = Y. | last2 = Coit | first2 = DG. | last3 = Woodruff | first3 = JM. | last4 = Brennan | first4 = MF. | title = Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. | journal = Ann Surg | volume = 217 | issue = 1 | pages = 72-7 | month = Jan | year = 1993 | doi =  | PMID = 8424704 | PMC = 1242736}}</ref>
#Fatty lymph nodes (esp. fatty hilus<ref name=pmid18337039>{{Cite journal  | last1 = Mack | first1 = MG. | last2 = Rieger | first2 = J. | last3 = Baghi | first3 = M. | last4 = Bisdas | first4 = S. | last5 = Vogl | first5 = TJ. | title = Cervical lymph nodes. | journal = Eur J Radiol | volume = 66 | issue = 3 | pages = 493-500 | month = Jun | year = 2008 | doi = 10.1016/j.ejrad.2008.01.019 | PMID = 18337039 }}</ref>) are less likely to harbor metastases.<ref name=pmid21972135>{{Cite journal  | last1 = Korteweg | first1 = MA. | last2 = Veldhuis | first2 = WB. | last3 = Mali | first3 = WP. | last4 = Diepstraten | first4 = SC. | last5 = Luijten | first5 = PR. | last6 = van den Bosch | first6 = MA. | last7 = Eijkemans | first7 = RM. | last8 = van Diest | first8 = PJ. | last9 = Klomp | first9 = DW. | title = Investigation of lipid composition of dissected sentinel lymph nodes of breast cancer patients by 7T proton MR spectroscopy. | journal = J Magn Reson Imaging | volume = 35 | issue = 2 | pages = 387-92 | month = Feb | year = 2012 | doi = 10.1002/jmri.22820 | PMID = 21972135 }}</ref>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Breast_carcinoma_in_a_lymph_node.jpg Breast carcinoma LN metastasis (WC)].
*[http://commons.wikimedia.org/wiki/File:Lymph_node_with_papillary_thyroid_carcinoma.jpg Thyroid carcinoma LN metastasis (WC)].
*[http://commons.wikimedia.org/wiki/File:Crc_met_to_node1.jpg Colorectal carcinoma LN metastasis (WC)].
 
Images (mimics):
*[http://commons.wikimedia.org/wiki/File:Decidua_in_a_lymph_node_-_low_mag.jpg Decidua in a LN - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Decidua_in_a_lymph_node_-_high_mag.jpg Decidua in a LN - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Endometriosis_lymph_node_-_2_-_intermed_mag.jpg Endometriosis in a LN - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Endosalpingiosis_in_lymph_node_-_intermed_mag.jpg Endosalpingiosis in a LN - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Endosalpingiosis_in_lymph_node_-_very_high_mag.jpg Endosalpingiosis in a LN - very high mag. (WC)].


==Kaposi sarcoma==
==Kaposi sarcoma==
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{{Main|Progressive transformation of germinal centers}}
{{Main|Progressive transformation of germinal centers}}
*Abbreviated as ''PTGC''.
*Abbreviated as ''PTGC''.
===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>{{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>
**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==
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**Rim of small (inactive) lymphocytes.
**Rim of small (inactive) lymphocytes.


IHC:
DDx:
*BCL2 -ve.
*[[Hodgkin lymphoma]] - with rare Reed-Sternberg cells.
*Non-Hodgkin [[lymphoma]].
**T-cell/histiocyte-rich large B cell lymphoma.


Image: [http://pleiad.umdnj.edu/hemepath/normal_node/normal_node.html Normal lymph node (umdnj.edu)].
Image: [http://pleiad.umdnj.edu/hemepath/normal_node/normal_node.html Normal lymph node (umdnj.edu)].
===IHC===
Screening panel:
*[[CD3]].
*[[CD5]].
*CD10.
*[[CD20]].
*CD30.
*CD15.
Others:
*BCL2 -ve.


==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}}
*Non-specific finding.
 
===Microscopic===
Features:<ref name=Ref_ILNP179>{{Ref_ILNP|179}}</ref>
*Sinuses distended with histiocytes - '''key feature'''.
*[[Plasma cell]]s increased.
 
DDx:
*[[Rosai-Dorfman disease]] - histiocyte nuclei large (~2-3x lymphocyte) and round with a prominent nucleoli.
 
===Sign out===
*The finding is often ignored; may be signed out as ''morphologically benign lymph nodes''.


==Kikuchi disease==
==Kikuchi disease==
*[[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>
*[[AKA]] ''Kikuchi-Fujimoto disease''.
*[[AKA]] ''Kikuchi-Fujimoto disease''.
===General===
{{Main|Kikuchi disease}}
*Rare disease that may mimic [[cancer]], esp. [[lymphoma]].
**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]].
**Have ''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:
*[[WC]]:
**[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)].
*www:
**[http://path.upmc.edu/cases/case200.html Kikuchi disease - several crappy images (upmc.edu)].
 
===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==
*[[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>
*Abbreviated '''CD'''.
*Abbreviated '''CD'''.
===General===
{{Main|Castleman disease}}
*Benign.
 
===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.
#*May be associated with [[follicular dendritic cell neoplasia]].<ref name=Ref_WMSP_596>{{Ref WMSP|596}}</ref>
#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====
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:
*[[WC]]:
**[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)].
*www:
**[http://path.upmc.edu/cases/case115.html CD HVV - case 1 - several images (upmc.edu)].
**[http://path.upmc.edu/cases/case301.html CD HVV - case 2 - several images (upmc.edu)].
 
====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==
*[[AKA]] ''Cat-scratch fever''.
*[[AKA]] ''cat scratch fever''.
===General===
{{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.
 
DDx of stellate abscess in lymph nodes - ''cat split'':<ref name=pmid>URL: [http://www.dermpathmd.com/mnemonics/mnemonics_dermatopathology.htm http://www.dermpathmd.com/mnemonics/mnemonics_dermatopathology.htm]. Accessed on: 23 September 2011.</ref>
*Cat-scratch disease.
*[[Sporotrichosis]].
*[[Lymphogranuloma venereum]].
*[[Tularemia]].
 
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)].
 
===Stains===
*Warthin-Starry stain +ve.
 
===IHC===
*B. henselae IHC stain +ve - '''diagnostic'''.


==Toxoplasma lymphadenitis==
==Toxoplasma lymphadenitis==
Line 482: Line 274:


==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.
 
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:
*[[Metastatic]] [[malignant melanoma]] - pigmented cells have nuclear atypia, not histiocytes.
 
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)].
 
===IHC===
*Interdigitating dendritic cells: S100 +ve, CD1a -ve.
*Langerhans cells: S100 +ve, CD1a +ve.


==Kimura lymphadenopathy==
==Kimura lymphadenopathy==
{{Main|Kimura disease}}
{{Main|Kimura disease}}
===Microscopic===
Features:
*Abundant eosinophils.
*Thick-wall blood vessels.


==Rosai-Dorfman disease==
==Rosai-Dorfman disease==
*Abbreviated ''RDD''.
*Abbreviated ''RDD''.
*[[AKA]] ''sinus histiocytosis with massive lymphadenopathy'', abbreviated ''SHML''.
{{Main|Rosai-Dorfman disease}}
==Langerhans cell histiocytosis==
{{Main|Langerhans cell histiocytosis}}
==Lymph node hyalinization==
*[[AKA]] ''hyalinized lymph node''.
===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.
Subdivided into:<ref name=pmid12973685/>
****Prominent nucleolus - visible with 10x objective.
*Mediastinal-type.
***Abundant cytoplasm.
**Usually in medullary sinus.
*Emperipolesis (from ''Greek'': ''em'' = inside, ''peri'' = around, ''polemai'' = wander about<ref>Stedman's Medical Dictionary. 27th Ed.</ref>):
**Onion peel-like appearance.
**Histiocytes contain other whole cells: neutrophils, lymphocytes, plasma cells.
*Pelvic-type hyalinization.
***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.
**Discrete round, eosinophilic, glassy appearance at low power, whirled/fibrous at high power.
***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>
**+/-Calcification.  


DDx:
DDx:
*Other histiocytosis:
*[[Amyloidosis]] - cotton candy-like appearance, usu. no calcifications.
**[[Langerhans cell histiocytosis]].
**[[Erdheim-Chester disease]].
*Infection, e.g. [[rhinoscleroma]] (nasopharynx), [[xanthogranulomatous pyelonephritis]].
*Xanthomatous change.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Emperipolesis_-_very_high_mag.jpg Emperipolesis in SHML (WC)].
**[http://commons.wikimedia.org/wiki/File:Rosai-Dorfman_disease_-_very_high_mag.jpg Rosai-Dorfman disease (WC)].
**[http://commons.wikimedia.org/wiki/File:Rosai-dorfman.jpg Rosai-Dorfman disease - S100 showing emperipolesis (WC)].
*www:
**[http://path.upmc.edu/cases/case318.html RDD - case 1 - several images (upmc.edu)].
**[http://path.upmc.edu/cases/case338.html RDD - case 2 - several images of breast (upmc.edu)].
**[http://path.upmc.edu/cases/case351/micro.html RDD - case 3 - several images (upmc.edu)].
**[http://path.upmc.edu/cases/case546.html RDD - case 4 - several images (upmc.edu)].


===IHC===
====Images====
*CD68 +ve.
<gallery>
*S100 +ve.
Image: Hyalinized lymph node -- intermed mag.jpg | Hyalinized LN - intermed. mag.
**Useful for seeing emperipolesis.
Image: Hyalinized lymph node - alt -- intermed mag.jpg | Hyalinized LN - intermed. mag.
*CD1a -ve.
Image: Hyalinized lymph node -- high mag.jpg | Hyalinized LN - high mag.
**CD1a positive in Langerhans cell histiocytosis.
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)].


==Langerhans cell histiocytosis==
===Sign out===
{{Main|Langerhans cell histiocytosis}}
*Not reported.
 
===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.


==See also==
==See also==

Revision as of 15:45, 5 March 2017

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

Kaposi sarcoma

  • One of the few non-lymphoid primary lymph node tumours.[3]

Melanocytic nevi

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

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.[4]

Microscopic

Features:[5]

  • 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:

Others:

  • BCL2 -ve.

Diffuse paracortical hyperplasia

General

  • Benign.

Microscopic

Features:[5]

  • 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.

Kikuchi disease

  • AKA histiocytic necrotising lymphadenitis (HNL).[6]
  • AKA Kikuchi-Fujimoto disease.

Systemic lupus erythematosus lymphadenopathy

Castleman disease

  • AKA angiofollicular lymph node hyperplasia, giant lymph node hyperplasia.[7]
  • Abbreviated CD.

Cat-scratch disease

  • AKA cat scratch fever.

Toxoplasma lymphadenitis

General

  • Caused by protozoan Toxoplasma gondii.

Microscopic

Features:[8]

  • 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

Kimura lymphadenopathy

Rosai-Dorfman disease

  • Abbreviated RDD.
  • AKA sinus histiocytosis with massive lymphadenopathy, abbreviated SHML.

Langerhans cell histiocytosis

Lymph node hyalinization

  • AKA hyalinized lymph node.

General

  • Benign.
  • Associated with aging.[9]

Microscopic

Features:

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

Subdivided into:[9]

  • 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

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. 174. ISBN 978-0781775960.
  5. 5.0 5.1 Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 179. ISBN 978-0781775960.
  6. 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.
  7. URL: http://www.mayoclinic.com/health/castleman-disease/DS01000. Accessed on: 17 June 2010.
  8. Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 113. ISBN 978-0781775960.
  9. 9.0 9.1 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.