Lymph nodes - not lymphoma
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Last revised 13 July 2006
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See also Lymphomas: B cell and plasma cell neoplasms and Lymphomas: non B cell
Table of contents
Primary references, images needed, embryology, normal anatomy, normal cell population, B cells, T cells, NK cells, mast cells, accessory immune system, normal development, age related changes
Inclusions, pigment, ectopic cells or tissue: adipose tissue, anthracosis, asbestos bodies, decidual reaction, endometriosis, epithelial, gold, iron, lipofuscin, megakaryocytes, melanosis, mesothelial, mullerian, nevus cells, prosthesis related, salivary gland, silicone, silicosis, smooth muscle, squamous epithelium, tattoo, thymus, thyroid follicles, yellow bodies
Primary immunodeficiency disorders: general, autoimmune lymphoproliferative syndrome, chronic granulomatous disease, CR3 deficiency, Omenn’s syndrome
Infectious/parasitic disorders: actinomyces, bacillary angiomatosis, bCG, brucellosis, Brugia, cat-scratch, Coccidiodes, Corynebacteria, denge fever, EBV, hemophilus influenza, herpes simplex, HHV6, HHV8/KSHV, histoplasmosis, HIV, Leishmania, leprosy, lymphogranuloma venereum, measles, mycobacteria-atypical, mycobacterial spindle cell pseudotumor, parvovirus B19, pseudofungi, syphilis, toxoplasmosis, tuberculosis, tularemia, vaccinia, Whipple’s disease, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis
Inflammatory disorders: reactive-general, acute nonspecific lymphadenitis, adult onset Still’s disease, allergic granulomatosis, amyloid, angiolymphoid hyperplasia with eosinophilia, Castleman’s disease, chronic lymphadenitis, Clofazimine, dermatopathic lymphadenitis, drug hypersensitivity, erythrophagocytosis, extramedullary hematopoiesis, follicular hyperplasia, granulomatous, hemophagocytic lymphohistiocytosis, hyaline deposits, infarction, inflammatory pseudotumor, Kawasaki, Kikuchi’s, Kimura’s disease, lipogranuloma, lymphedema, mantle cell/marginal zone hyperplasia, monocytoid B cell hyperplasia, plasmacytosis, polykaryocytes, post-lymphangiography granuloma, post-transplant, progressive transformation of germinal centers, rheumatoid arthritis, sarcoidosis, sinus histiocytosis, sinus histiocytosis with massive lymphadenopathy, Sjogren’s syndrome, SLE, systemic sclerosis, vascular transformation of sinuses, vasculitis, venolymphatic angiodysplasia
Neoplasms (not lymphoma): ALL, AML, angioimmunoblastic lymphadenopathy, angiolipomatous hyperplasia, angiomyolipoma, angiomyomatous hamartoma, angiosarcoma, CML, epithelioid hemangioendothelioma, Erdheim-Chester disease, fibroblastic reticulum cell sarcoma, follicular dendritic cell sarcoma, hemangioma, histiocytic sarcoma, indeterminate cell tumors, interdigitating dendritic/reticulum cell sarcoma, Kaposi’s sarcoma, Langerhans cell histiocytosis, leiomyoma, lymphangioma, lymphangiomyomatosis, lymphoma, malignant histiocytosis, mastocytosis, metastases to lymph nodes, myofibroblastoma, plasmacytoma
Miscellaneous: grossing, lymph node dissection
American Journal of Clinical Pathology (AJCP), August 1975 to May 2006
American Journal of Pathology (free after 6 months), January 1990 to June 2006
American Journal of Surgical Pathology (AJSP), March 1977 to June 2006
Archives of Pathology and Lab Medicine (Archives), January 1976 to May 2006
BMC Clinical Pathology, 20 June 2001 to 23 May 2006
Human Pathology (Hum Path), March 1970 to June 2006
Journal of Clinical Pathology (free after 1 year) Sept 1965 to June 2006
Modern Pathology (Mod Path), January 1988 to June 2006
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); Mosby, 2004
Sternberg,
S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins,
2004
Sternberg: Histology for Pathologists (2nd Ed); 1997
University of Pittsburgh Medical Center Case Reports, cases 1-470
Warnke: Tumors of the Lymph Nodes and Spleen (Atlas of Tumor Pathology, 3rd Series, Vol. 14; 1995)
Journal search terms: lymph node
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Images are particularly needed for these topics: in lymph node - marginal zone, centroblasts, centrocytes, B cells, T cells, NK cells, macrophages, mast cells, dendritic cells (all types, also EM), littoral cells, CR3 deficiency, Brugia, HIV, mycobacterial spindle cell pseudotumor, parvovirus, pseudofungi, syphilis, vaccinia, Yersinia (all species), amyloid, chronic lymphadenitis, clofazimine, extramedullary hematopoiesis, hyaline deposits, Kawasaki disease, lipogranuloma, lymphedema, mantle cell/marginal zone hyperplasia, monocytoid B cell hyperplasia, Sjogren’s syndrome, vasculitis, angiolipomatous hamartomas, angiomyomatous hamartoma
Develop from lateral plate mesoderm (on either side of intermediate mesoderm)
First, lymphatic sacs arise from endothelial outgrowths of large central veins at week 5
Second, lymphatic plexus develops from lymphatic sacs
Third, plexuses are invaded by mesenchymal cells that proliferate and aggregate to form lymph nodes
Small collections of lymphoblasts are present by first trimester
By second trimester, cortex is distinguishable from medulla and primary follicles are present
References: Human Anatomy - Pearson
Normal anatomy/histology of lymph node
A secondary lymphoid organ (where B and T cells proliferate in response to exogenous antigen)
Primary lymphoid organs are bone marrow and thymus
Other secondary lymphoid organs are spleen and Peyer’s patches
Tertiary lymphoid organs are tissues with few lymphocytes that recruit more when inflammation is present
Lymph nodes are organized to detect and inactivate foreign antigens present in lymph fluid that drains skin, GI tract and respiratory tract, the major organs in contact with the environment
Gross: ovoid with gray-tan cut surface
Micro: at low power, lymph node structures are capsule, cortex and medulla, follicles, paracortex, sinuses
Afferent lymph vessels: penetrate capsule, enter marginal sinus, communicate with intranodal sinuses, then become efferent vessels, which lack an endothelial lining; intranodal vessels contain littoral cells or histiocytes with phagocytic properties
Capsule: thin fibrous connective tissue covering of lymph node; may be thicker at hilus; connected to fibrous trabeculae which penetrate the node; capsule may contain smooth muscle cells (Anat Rec 1975;183:517)
Cortex: subcapsular portion of node with largest number of follicles
Germinal center: contains centroblasts and centrocytes; also macrophages and follicular dendritic cells; surrounded by a mantle zone of small B lymphocytes (which resembles the primary follicle, see below)
Positive stains: strong and dense bcl6 and CD10
Negative stains: bcl2
Mantle zone: small B cells surrounding pale staining germinal centers
Marginal zone: light zone on outer rim of mantle zone; contains post-follicular memory B cells derived after stimulation of recirculating cells from T cell dependent antigen
Medulla: portion of node closest to hilum; contains vessels and sinuses and mast cells but minimal number of follicles
Medullary cords: found in hilar region between the sinuses, composed mostly of small B and T lymphocytes
Paracortex: tissue between cortical follicles and medulla; mostly dark staining; contains post-capillary venules (lined by high endothelial cells with intraendothelial lymphocytes), dendritic cells and T cells; expands during cell-mediated immunological reactions; has coarse network of reticulin fibers
Primary follicle: round aggregates of small, dark staining lymphocytes, usually near the capsule, within a network of follicular dendritic cell processes; no germinal center present
Secondary follicle: arise from primary follicles that develops germinal centers (see below) due to antigenic stimulation of B cells and production of antibodies; contains pale staining germinal center which may be polarized towards site of antigen entry; contains B cells, follicular dendritic cells (CD21+, CD35+) and tingible body macrophages
Sinuses: carry lymph from afferent to efferent lymphatics; subcapsular sinus is below capsule and partially lined by endothelium; becomes “medullary” as it approaches the hilum and is lined by macrophages
Vessels: blood enters and leaves lymph node at hilus
Normal cell population of lymph node
See also specific cell types below
Centroblasts: large non-cleaved follicular center cells (B cells) with moderate amounts of basophilic cytoplasm, large round nuclei, open chromatin, multiple peripheral nucleoli; frequent mitotic figures
Centrocytes: large and small cleaved follicular center cells (B cells) with scant cytoplasm and inconspicuous nucleoli
Plasma cells: abundant basophilic cytoplasm (due to high content of rough endoplasmic reticulum) with paranuclear hof (highlighted by Giemsa stain, due to Golgi apparatus); have eccentrically placed nucleus with spoke wheel (clock face) chromatin due to small clumps of chromatin on nuclear membrane in an otherwise round and clear nucleus; may have Russell bodies (intracytoplasmic PAS+ globules)
Develop from stem cells of yolk sac, fetal liver, spleen and bone marrow
B cells mediate reactions to lipopolysaccharides and other macromolecules with repetitive features
B cells express surface immunoglobulin (Ig), which is composed of 2 heavy (H) and 2 light (L) chains (either kappa or gamma)
B cell antigen receptor loci may have 4 types of modification - (1) recombination of variable, diversity and joining regions (VDJ); (2) somatic hypermutation of V segments; (3) immunoglobulin heavy chain gene class switching; and (4) receptor editing
Early B cell precursor is TdT+, CD34+, HLA-DR+; then undergoes heavy (H) chain rearrangement and adds CD19; then adds CD10; then adds IgM heavy chain; then adds light (L) chain rearrangement and adds cytoplasmic IgM with heavy and light chains; then expresses IgM and IgD with the same binding site; then adds CD20 (now called preB cell); then adds surface Ig; then adds CD21 and CD22 and drops TdT (now called B cell)
If B cell encounters an antigen that interacts with its variable region, it becomes a plasma cell
Precursor B cells contain immunoglobulin related components but not immunoglobulin; express CD179a and CD179b (precursor to light chains) as part of their pre-B cell receptor, which disappears when replaced with conventional light chains
B cells express surface immunoglobulin, which is associated with CD79a/CD79b complex to form a B cell antigen receptor complex
IgH (heavy chain of immunoglobulin): encoded at 14q32; variable portion coded by VDJ genes
IgL (light chain of immunoglobulin): kappa on 2p11, lambda on 22q11; no diversity region is present
Heavy chain isotype switch: determines if immunoglobulin is IgM, IgD, IgG1-4, IgA1-2 or IgE (9 constant regions); mediated by switch genes
B cell lymphomas: clonal light chain rearrangement is usually specific for the presence of a B cell neoplasm
Micro: mainly present in primary and secondary follicular centers
References: B cell antigen presentation, B cell differentiation
Develop from bone marrow, become prothymocytes, then migrate to thymus gland, where self-recognizing T cells are eliminated
T cell receptors (TCR) are either alpha/beta (95%) or gamma/delta (5%) heterodimers
T cells mediate reactions to soluble antigens and some particulate antigens
Precursor cell is TdT+, CD34+, HLA-DR+; then drops HLA-DR; then adds CD2, CD5, CD7 (early thymocyte) while undergoing gamma/beta chain rearrangement; then adds CD1 and drops CD34; now a common thymocyte; then undergoes beta/alpha chain rearrangement and adds CD4 and CD8; then splits into helper or cytotoxic T cell, without TdT, CD1, CD5 and CD7; has CD2, CD3, CD4 (helper) or CD8 (cytotoxic)
T alpha and delta genes are on 14q11; T beta is on 7q34; T gamma is on 7p15 (note: there are only 10 V regions, so a polyclonal population of cells can appear oligoclonal)
90% of peripheral T-cell lymphomas have rearrangements of T-alpha, beta and gamma genes, including all cases of mycosis fungoides and Sezary syndrome
Note: T cell clonality is seen in AIDS and congenital immunodeficiency syndromes, but does NOT indicate malignancy
Note: rarely a clonal band may comigrate with the germline band; solution - use 2-3 restriction enzymes (HindIII, EcoRI, BamHI)
Note: T cells and NK cells arise from a common progenitor that expresses CD3 epsilon and cannot develop into B cells
Micro: mainly present in paracortex of lymph node; little cytoplasm, small, round/irregular nuclei with dark and condensed chromatin; may have blastic forms with moderate cytoplasm, irregular nuclei and marginal nucleoli
NK cells (Natural Killer cells)
Distinct group of non-T, non-B lymphocytes
Capable of lysing certain target cells without prior activation or major histocompatibility complex restriction
Believed important in defense against viral and bacterial infections and tumor cells as well as immunomodulation and regulation of hematopoiesis
Granules contain perforin (forms pores in cell membrane of target cells through which granzymes enter and induce apoptosis)
Activated by interferons or cytokines
Comprise 5-20% of peripheral blood lymphocytes
If target cell has class I MHC, then NK cell's killer cell inhibitory receptor (KIR) inhibits cytolysis
Micro: large granular lymphocytes
Positive stains: CD56 (>90%, adhesion molecule), CD57 (unknown
function), CD16 (>90%, low affinity IgG Fc receptor / FC
RIII that is
responsible for antibody dependent cellular cytotoxicity in NK cells and also
expressed on neutrophils and monocyte subset); also cytoplasmic (not surface)
CD3, CD2, CD7, CD8, CD11b, CD11c, perforin, granzyme B, TIA-1
Negative stains: CD3 (surface), immunoglobulins
See also discussion in Spleen chapter
Present in T cell areas (World J Surg Oncol 2003;1:25)
Micro: difficult to detect; distinct cytoplasmic boundaries, faintly granular cytoplasm, large pale nuclei; some cells are elongated and resemble fibroblasts
Positive stains: Giemsa and toluidine blue (purple granules), Leder stain, microphthalmia transcription factor, tryptase; also CD2, CD25, CD45, CD68, CD117
Includes antigen presenting cells (dendritic cells and Langerhans cells) and antigen processing cells (monocytes, macrophages)
Histiocytes: monocytes, macrophages, Langerhans cells and dendritic cells
Fibroblastic reticulum cells
Stromal support cells
Micro: spindled cells in the parafollicular and deep cortex
Positive stains: vimentin, smooth muscle actin, desmin, alkaline phosphatase, CD68 (focal), keratin (some)
Negative stains: CD21, CD35, S100, EBV
EM: filaments with focal condensations
Follicular dendritic cells
Associated with germinal centers
Have complex cell processes joined by desmosomes, but no Birbeck’s granules
Control B cell maturation and isotype switching
FDC like cells can be produced from monocytes (BMC Immunol 2005;6:23)
Upregulated by Tamoxifin treatment for breast cancer (Am J Pathol 2003;163:1313)
Positive stains: CD21, CD35; also fascin, ER, epidermal growth factor receptor, CD11b, CD14, CD19, CD20; variable S100, EBV, CD68
Negative stains: CD1a, keratin
Interdigitating dendritic cells
Associated with interfollicular (T cell) zones in lymphoid tissue
Micro: may cause the paracortex to look mottled; resemble Langerhans cells; abundant, clear and pale cytoplasm with ill defined borders; have large and bizarre nucleus with deep clefts and folds; delicate almost transparent chromatin, inconspicuous nucleoli
Positive stains: S100, vimentin, fascin, CD45RB, CD68 (focal), variable CD1a (AJSP 1998;22:1048, AJCP 2001;115:589); also CD13
Negative stains: CD21, CD35, B and T cell markers, actin, desmin, keratin
EM: have complex cell processes that interdigitate with T cells, but NO desmosomes and NO Birbeck granules
Indeterminate cells
Resemble Langerhans cells but NO Birbeck’s granules
Derived from Langerhans cells or interstitial dendritic cells, reside in skin and mucosa
Migrate into local lymphoid tissue after antigen capture
Positive stains: CD1a, S100, fascin
Interstitial dendritic cell
Counterpart of Langerhans cell in parenchymal organs (excluding cornea and brain)
Langerhans cells
Related to interdigitating dendritic cells and dermal dendrocytes
Positive stains: CD1a, S100, vimentin, Langerin, variable CD68
Negative stains: CD21, CD35 and CD86
EM: Birbeck’s granules
Macrophages
Process antigens via phagocytosis
Related to circulatory monocytes
Are present throughout the lymph node
May contain thyroglobulin in lymph nodes draining thyroid tumors (J Clin Pathol 2001;54:314)
Micro: abundant cytoplasm with medium to large nuclei with vesicular chromatin; tingible body macrophages have clear cytoplasm and contain apoptotic bodies, which gives node a starry sky pattern
Positive stains: CD68, lysozyme
Sinus lining cells
Also called littoral cells, particularly in spleen
Have endothelial and macrophage properties
Normal lymphoid cells undergo rearrangements within their antigen receptor genes, causing specificity for the immunoglobulin or T cell receptor that they produce
Monoclonal proliferations are presumed to be neoplastic; polyclonal populations are not
Apoptosis helps eliminate B cells producing antibodies with low avidity
Lymphoid stem cell: TdT+, CD34+, HLA-DR+, then develops along B or T cell pathway
Age related changes in lymph nodes
Germinal centers are more common in infants and children, decrease in young adults, often absent in elderly
Germinal centers are more common in mesenteric and cervical lymph nodes
Hyaline deposits increased with age
Peripheral lymph nodes, with little antigenic stimulation, often have replacement by fat, particularly in axillary, cubital and popliteal nodes
Lymphocyte depletion, fibrosis and hyaline deposits are associated with chronic disease, particularly cancer
References: Am J Pathol 1975;78:7, J Clin Pathol 1980;33:454
Inclusions, pigment or ectopic cells or tissue
Adipose tissue metaplasia in lymph nodes
Very common, particularly in external iliac and obturator nodes (see also Age related changes)
May cause masses up to 10 cm
Common in intrapulmonary lymph nodes
Due to coal dust, smoke or pollution
May be associated with storiform pattern of histiocytes that resembles a neoplasm (Hum Path 1998;29:851)
Associated with silica, although often no history of industrial exposure
Associated with hyalinization in nodes of elderly Japanese (Histol Histopathol 2003;18:1169)
Case reports: causing mediastinal lymphadenopathy resembling TB (Eur J Intern Med 2003;14:444)
Micro: fine anthracotic pigment; may be associated with storiform pattern of spindle cells that extend outside capsule and surround nerve; also nodal hyaline scars and polarizable material suggestive of silica
Positive stains: CD68 (macrophages containing pigment)
DD: MFH, follicular dendritic cell tumor, spindle cell melanoma, Kaposi’s sarcoma
Presence of asbestos bodies in hilar lymph nodes after bleach digestion correlates with heavy lung burden (Mod Path 1990;3:513)
Thoracic lymph node may have higher asbestos burden than lung in non-occupationally exposed individuals (Am J Ind Med 2000;37:169)
Asbestosis in asbestos exposed individuals is associated with mediastinal adenopathy (Clin Radiol 1992;45:340)
Decidual reaction / ectopic decidua in lymph nodes
Rare
Often discovered in pregnant woman with cervical squamous cell carcinoma requiring hysterectomy and lymphadenectomy
A particular problem differentiating from squamous cell carcinoma during frozen section (Archives 2005;129:e117)
Derive from endometriosis or mesenchymal cells under the influence of pregnancy hormones
Case reports: lymph node with decidua and metastatic squamous cell carcinoma (J Surg Oncol 1988;38:126)
Gross: compact mass in lymph node
Micro: subcapsular or superficial cortical nodules of relatively uniform, loosely cohesive cells with distinct cell membranes, abundant amphophilic cytoplasm with variable vacuoles, round vesicular nuclei and occasional nucleoli; may have occasional bizarre, hyperchromatic nuclei; no intercellular bridges, no dyskeratosis, no keratin pearls, no mitotic activity, no desmoplasia
Negative stains: keratin
DD: metastatic squamous cell carcinoma (small, irregular nests with well circumscribed borders of tightly cohesive, polygonal cells with small, dark staining nuclei and pleomorphism)
Not common
May cause enlargement of lymph nodes
Case report: woman in 40’s with ileocecal valve and nodal involvement by endometriosis
Micro: endometrial type glands and stroma, usually within center of node; may undergo decidual reaction; variable hemorrhage; rarely has smooth muscle component
Positive stains: keratin, EMA, ER, PR, CD10 (stroma)
Epithelium inclusions in lymph nodes
May coexist with breast micrometastases
In axilla, may be due to pre-sentinel lymph node biopsy breast massage (AJSP 2004;28:1641)
Case reports: squamous epithelial cyst in axillary node removed for lobular breast carcinoma (Archives 2004;128:361), benign cystic epithelial choristoma in celiac node (Hum Path 1987;18:866)
Micro: single or tubules of epithelial cells in subcapsular sinus of draining lymph node after surgical or needle manipulation; also hemosiderin laden macrophages and damaged erythrocytes; breast epithelial inclusions may show apocrine metaplasia, sclerosing adenosis, epithelial hyperplasia
Positive stains: breast - myoepithelial markers (p63, S100, smooth muscle actin)
DD: metastatic carcinoma
References: AJCP 2000;113:259, AJSP 2003;27:513; Archives 2003;127:e25 (axillary inclusions)
Case reports: 34 year old woman with gold injections for rheumatoid arthritis (J Clin Pathol 2001;54:562), simulating microcalcifications on mammogram (Hum Path 1988;19:992)
Micro: reactive node with variable infarction
DD: lymphoma
Case reports: 49 year old woman with lymphadenopathy after single infusion of iron dextran (J Clin Pathol 1968;21:492)
Portal lymphadenopathy due to lipofuscin pigment is associated with primary biliary cirrhosis and other chronic cholestatic conditions (J Clin Pathol 1989;42:1160)
Micro: lipofuscin pigment present in sinus histiocytes
Often associated with extramedullary hematopoiesis when present in lymph nodes
Case reports: mimicking metastatic breast carcinoma in axillary node (Archives 2002;126:618)
Positive stains: CD31, CD61, vWF
Negative stains: keratin, CD68
DD: multinucleated histiocytes (larger, more cytoplasm, vesicular nuclei that are not multilobated, CD68+)
Yellow brown spindle bodies in mesenteric nodes may be due to melanosis coli (Histopathology 1978;2:47)
Case reports: presence in colonic mucosa and pericolonic lymph nodes (Archives 2004;128:565)
Mesothelial cell inclusions in lymph nodes
Rare
Usually mediastinal or abdominal lymph nodes (Mod Path 1996;9:879)
Often missed on routine H&E sections (AJSP 1999;23:1264)
Hyperplastic mesothelial cells in nodal tissue may derive from reactive serosal mesothelium that is dislodged into draining lymphatics (Archives 2000;124:609); often associated with serosal fluid collection (pericardial, pleural, abdominal) at time of nodal biopsy (Hum Path 1998;29:339), including episodes of intraperitoneal hemorrhage and ascites (Pathology 2001;33:239), perhaps because effusion allows for mesothelial cell migration into lymphatics (Diagn Cytopathol 2003;29:163)
Micro: single cells or small clusters of cells in nodal sinuses with well defined cells borders and mesothelial windows, abundant cytoplasm, bland nuclei; no mitotic figures
Positive stains: keratin (perinuclear)
Negative stains: EMA, CD15, CEA, B72.3
EM: long microvilli
DD: metastatic carcinoma or mesothelioma
References: AJCP 1990;93:741
Mullerian inclusions / cysts in lymph nodes
Also called endosalpingiosis
Pelvic lymph nodes of women, also rarely mediastinal and pelvic nodes in males
Present in 5-41% of intra-abdominal nodes of women (Am J Obstet Gynecol 1978;130:813), 20% of women with gynecologic malignancies in paraaortic/pelvic nodes (Gynecol Oncol 2000;78:242)
May be due to metaplastic proliferation of peritoneal mesothelium
May represent metastatic ovarian serous borderline tumors, particularly if present in nodes that drain ovary (AJSP 2000;24:710), although no definite prognostic significance (AJSP 2006;30:614)
May have endometriotic foci elsewhere (Archives 2005;129:e218)
Case report: 64 year old woman with endosalpingiosis and psammoma bodies in intramammary lymph node presenting as mammographic calcifications (Archives 1995;119:841)
Micro: capsular or parenchymal involvement by small round glands or cysts lined by bland, serous (mullerian), cuboidal-columnar epithelium with simple architecture; psammoma bodies are common; may undergo squamous metaplasia; no/rare mitotic figures, no/mild atypia, no desmoplastic stroma, no endometrial stroma
Positive stains: mucin
DD: metastatic adenocarcinoma (atypia, desmoplasia, mitosis, usually no ciliated cells)
Incidence in axillary nodes is 7% per patient and 0.5% per node in one study (AJCP 1994;102:102)
Presence in sentinel nodes in melanoma patients is associated with cutaneous nevi (AJCP 2004;121:58) and congenital cutaneous nevi (Am J Dermatopathol 2002;24:1)
May represent benign metastases from intradermal nevus in area of lymphatic drainage (AJCP 1985;84:220)
Micro: single cells, linear arrangements or aggregates of small, round/oval nevus cells with moderate pale/clear cytoplasm, round nuclei with fine chromatin, no prominent nucleoli or pleomorphism, usually within fibrous capsule and trabeculae, but also within nodal parenchyma (AJSP 2003;27:673) or surrounding a small vessel (AJSP 1996;20:834); no angiolymphatic invasion, no mitotic figures, no prominent melanin pigment
Cytology: nodules of uniform nevoid cells, but also possibly atypical melanocytic cells from dermatopathic lymphadenopathy (Diagn Cytopathol 2004;31:180)
Positive stains: S100, MART1, tyrosinase, p16 (Virchows Arch 2003;443:745)
Negative stains: HMB45 (occasionally is very focal), Ki-67 (<1%)
DD: metastatic carcinoma or melanoma (usually not confined to capsule, atypia, mitotic figures, different immunostaining), Spitz nevus (larger cells with abundant eosinophilic cytoplasm, vesicular nuclei with prominent nucleoli), blue nevus (also spindled/dendritic cells with heavy pigmentation)
References: AJSP 2002;26:1351 (immunostains)
Blue nevus
May be incidental in axillary node dissection for breast carcinoma (AJSP 1984;8:907)
May be associated with blue nevus in regional skin (Histopathology 1977;1:451)
May need to bleach sections
Case reports: blue nevus of nodal capsule #1 (