Lymph node pathology

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:

• 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	S100+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	S100+, CD1a+	Kimura disease (eosinophilia), Rosai-Dorfman disease	LCH - very high mag.
Rosai-Dorfman disease	sinus histiocytosis	emperipolesis (intact cell within a macrophage)	S100+, 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:

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

Lymph node metastasis

General

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

Gross

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

Microscopic

Features:

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

Notes:

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

DDx - mimics of metastatic disease:

• Endometriosis.
• Ectopic decidua.
• Endosalpingiosis.
• Melanocytic nevus - intracapsular or within the trabeculae.
• Dermatopathic lymphadenopathy.^{[citation needed]}
• Sinus histiocytosis - especially for the junior resident.
• Tumour deposit (discoutinuous extramural extension) - definition dependent on primary tumour (e.g. in the head & neck they are tumour replaced lymph nodes, in the colon they are considered separate and not counted as lymph nodes).

Images

• 

  Breast carcinoma LN metastasis (WC)

• 

  Thyroid carcinoma LN metastasis (WC)

• 

  Colorectal carcinoma LN metastasis (WC)

• 

  Melanoma in a lymph node. (WC)

Mimics

• 

  Decidua in a LN - low mag. (WC)

• 

  Decidua in a LN - high mag. (WC)

• 

  Endometriosis in a LN - intermed. mag. (WC)

• 

  Endosalpingiosis in a LN - intermed. mag. (WC)

• 

  Endosalpingiosis in a LN - very high mag. (WC)

Kaposi sarcoma

Main article: Kaposi sarcoma

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

Melanocytic nevi

Main article: Melanocytic lesions

See: Dermatopathic lymphadenopathy.

• Benign melanocytic nevi can be found in lymph nodes.

Progressive transformation of germinal centers

Main article: 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.

Microscopic

Features:

• 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:

• Hodgkin lymphoma - with rare Reed-Sternberg cells.
• Non-Hodgkin lymphoma.
  • T-cell/histiocyte-rich large B cell lymphoma.

Image: Normal lymph node (umdnj.edu).

IHC

Screening panel:

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

Others:

• BCL2 -ve.

Diffuse paracortical hyperplasia

General

• Benign.

Microscopic

Features:

• 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).
• AKA Kikuchi-Fujimoto disease.

Main article: Kikuchi disease

Systemic lupus erythematosus lymphadenopathy

General

• Lymphadenopathy associated with systemic lupus erythematosus (SLE).

Microscopic

Features:

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

DDx:

• Kikuchi disease.

Images

• 

  SLE lymphadenopathy - high mag. (WC)

• 

  SLE lymphadenopathy - very high mag. (WC)

Castleman disease

• AKA angiofollicular lymph node hyperplasia, giant lymph node hyperplasia.
• 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:

• 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:

• Toxoplasmosis - low mag. (WC).
• Toxoplasmosis - high mag. (WC).

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.

Microscopic

Features:

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

Subdivided into:

• 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

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  Hyalinized LN - intermed. mag.

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  Hyalinized LN - intermed. mag.

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  Hyalinized LN - high mag.

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  Hyalinized LN - very high mag.

www:

• Lymph node with amyloidosis - several images (flickriver.com).

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• Not reported.

See also

• Haematopathology.