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==
===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}}
*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.
*[[Dermatopathic lymphadenopathy]] - histiocytes have (melanin) pigment.
 
===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 483: Line 242:


==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]] - (melanin) pigmented cells have nuclear atypia, not histiocytes.
*[[Sinus histiocytosis]] - no cells with melanin.
 
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''.
===General===
*[[AKA]] ''sinus histiocytosis with massive lymphadenopathy'', abbreviated ''SHML''.
*[[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>
{{Main|Rosai-Dorfman disease}}
*Super rare.
*Prognosis - good.
 
===Microscopic===
Features:
*Sinus histiocytosis:
**Histiocytes - abundant.
***Singular large round nuclei<ref>Bailey, D. 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>
 
DDx:
*Other histiocytosis:
**[[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===
*CD68 +ve.
*S100 +ve.
**Useful for seeing emperipolesis.
*CD1a -ve.
**CD1a positive in Langerhans cell histiocytosis.


==Langerhans cell histiocytosis==
==Langerhans cell histiocytosis==
{{Main|Langerhans cell histiocytosis}}
{{Main|Langerhans cell histiocytosis}}
===Microscopic===
Features:
*Langerhans cells histiocytes - '''key feature'''.
**Clusters of cells (histiocytes) with a reniform (kidney-shaped) nucleus and abundant foamy cytoplasm.
*+/-Eosinophils - often prominent.
See ''[[Langerhans cell histiocytosis]]'' for details.


==Lymph node hyalinization==
==Lymph node hyalinization==
Line 599: Line 276:
*[[Amyloidosis]] - cotton candy-like appearance, usu. no calcifications.
*[[Amyloidosis]] - cotton candy-like appearance, usu. no calcifications.


Images:
====Images====
<gallery>
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)].
*[http://www.flickriver.com/photos/euthman/sets/72157594513987154/ Lymph node with amyloidosis - several images (flickriver.com)].
===Sign out===
*Not reported.


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

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
Error creating thumbnail:
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
Error creating thumbnail:
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
Error creating thumbnail:
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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