Diagnostic Pathology Ashton.3rd Edition(2016) ■■■【1】Handling of lymph node biopsy Figure 1.1 Series of sections from a fine needle aspiration cell block preparation demonstrating the use of 'spare sections' between haematoxylin and eosin (H&E) levels for immunohistochemistry ■■■【2】Reactive lymph node structure Figure 2.1 Low-power view of a reactive lymph node. Note the irregularity of size and shape of the reactive follicles, which have well-defined mantles. The subcapsular sinus and some medullary sinuses are recognizable Figure 2.2 High-power view of a reactive germinal centre containing tingible body macrophages and showing zonation of centrocytes and centroblasts Figure 2.3 Imprint preparation of a reactive lymph node showing centroblasts with basophilic cytoplasm and visible nucleoli. The smaller lymphoid cells are a mixture of centrocytes and T-cells Figure 2.4 Plastic-embedded section of a reactive follicle showing centroblasts with visible nucleoli together with smaller centrocytes, a few of which show cleft nuclei Figure 2.5 Regressing reactive germinal centre consisting mainly of centrocytes. The nuclei of several dendritic reticulum cells are present; mononuclear, binuclear and multinucleated cells are highlighted with arrows. These have oval nuclei with a well-defined nuclear membrane and a single eosinophilic nucleolus. These nuclei appear singly, in pairs or as small clusters Figure 2.6 Reactive germinal follicle stained for immuno- globulin M (IgM). Note the positive staining of mantle cells and deposition of IgM, in the form of immune com- plexes, on follicular dendritic cells Figure 2.7 Reactive germinal follicle stained for CD21 to show follicular dendritic cells Figure 2.8 Reactive germinal follicles stained for CD79a. Note the well-defined, strongly stained mantle zones Figure 2.9 High-power view of a reactive germinal follicle showing the germinal centre cells (left), mantle cells (centre) and marginal zone cells with increased clear cytoplasm (right) Figure 2.10 Reactive lymph node stained by the Gordon and Sweet method to show reticulin. Note the vascularity of the paracortex Figure 2.11 Paracortex of a reactive lymph node stained by the periodic acid-Schiff (PAS) technique. PAS-positive staining outlines a high endothelial venule containing many small lymphocytes in the lumen Figure 2.12 Plastic-embedded section from the paracor- tex of a reactive lymph node showing a high endothelial venule. Note the lymphocyte that appears to be passing between endothelial cells Figure 2.13 Section of paracortex showing many interdigi- tating reticulum cells. The twisted grooved nuclei of these cells have an appearance said to resemble a 'wrung-out dish- cloth'. They have abundant, ill-defined, pale pink cytoplasm Figure 2.14 Electron micrograph of interdigitating reticulum cells. Note the complexity of the nuclear shape and the interdigitating cell membranes that give this cell its name Figure 2.15 Sinus lining cells showing oval or bean- shaped nuclei with inconspicuous nucleoli and abundant pale-staining cytoplasm Figure 2.16 High-power view of an island of plasmacytoid monocytes. Note the regular rounded nuclei of these cells and their amphophilic cytoplasm. Many apoptotic cells are present together with two 'tingible body' macrophages Figure 2.17 Section of reactive lymph node stained for CD3. Note scattered T-cells in the reactive follicle (right) and more closely packed T-cells in the paracortex (left). The island of plasmacytoid monocytes is unstained Figure 2.18 Island of plasmacytoid monocytes stained for CD68. Note strong granular staining of the plasmacy- toid monocytes and strong staining of a 'tingible body' macrophage Figure 2.19 Section of reactive lymph node showing two follicles and an island of plasmacytoid monocytes (arrow) ■■■【3】Reactive lymph node patterns ■■■【4】Rheumatoid lymphadenopathy Figure 3.1 Rheumatoid lymphadenopathy: lymph node stained with methyl green pyronin. The node shows follicular hyperplasia with numerous red (pyroninophilic) plasma cells in the medullary cords Figure 3.2 Rheumatoid lymphadenopathy: lymph node stained by Giemsa stain. The deep basophilia of the plasma cell cytoplasm highlights these cells in the medullary cords Figure 3.3 'Gold lymphadenopathy'. Axillary lymph node from a patient with rheumatoid disease treated with colloidal gold. Black pigment is seen within histiocytes Figure 3.4 'Gold lymphadenopathy' viewed in polarized light showing characteristic orange-red birefringence ■■■【5】Syphilis Figure 3.5 Secondary syphilis. Lymph node showing marked follicular hyperplasia with small epithelioid granulomas in the paracortex Figure 3.6 Secondary syphilis. Lymph node showing epithelioid cell clusters in the paracortex adjacent to a reactive follicle Figure 3.7 Syphilitic lymph node showing marked venulitis with giant cells ■■■【6】Tocoplasma Figure 3.8 Toxoplasmosis. Lymph node showing marked follicular hyperplasia and numerous small epithelioid cell clusters Figure 3.9 Toxoplasmosis. The epithelioid cell clusters appear to encroach on and enter the germinal centres. A collection of monocytoid B-cells is seen between the two germinal centres Figure 3.10 Toxoplasmosis. Prominent monocytoid B-cells distributed in and around a sinus ■■■【7】Kimura disease Figure 3.11 Kimura disease. Lymph node shows follicular hyperplasia. One follicle shows necrosis and an eosinophil microabscess Figure 3.12 Kimura disease. High-power view of the follicle containing an eosinophil microabscess Figure 3.13 Kimura disease. Follicle centre largely replaced by eosinophils and amorphous eosinophilic material. Also shown, by the arrow, is a follicular dendritic cell polykaryon ■■■【8】HIV Figure 3.14 Human immunodeficiency virus lymphadenopathy. Lymph node showing follicular hyperplasia with large irregular germinal centres. Islands of pale-staining monocytoid B-cells can be seen in the centre of the field Figure 3.15 Human immunodeficiency virus lymphade- nopathy. High-power view showing part of a germinal centre and an island of monocytoid B-cells ■■■【9】Progressive transformation Figure 3.16 Progressive transformation of germinal centres. Section showing a 'transformed' expanded germinal centre with adjacent reactive lymphoid follicles Figure 3.17 Progressive transformation of germinal centres. Section stained for CD79a showing strong positive staining of mantle cells. The 'transformed' follicle is expanded and broken up by mantle cells. Staining for immunoglobulin D would show a similar appearance Figure 3.18 Progressive transformation of germinal centres. Section stained for CD21 showing follicular dendritic cells. The 'transformed' follicle shows an expanded network of follicular dendritic cells in compari- son with the tight networks seen in the adjacent reactive follicles ■■■【10】Castleman Figure 3.19 Castleman disease, hyaline vascular type. Note hyalinized follicles and lack of sinus structures Figure 3.20 Castleman disease, hyaline vascular type. Follicle showing hyalinization of the germinal centre with penetrating vessels, onion-skin layering of the mantle cells and vascularized interfollicular tissue Figure 3.21 Castleman disease, plasma cell variant. Reactive follicles in a background of plasma cells. No sinus structure visible Figure 3.22 Castleman disease, plasma cell variant. Hyalinized follicle composed mainly of dendritic and endothelial cells surrounded by plasma cells Figure 3.23 Giemsa-stained section of Castleman disease plasma cell variant. This case showed kappa light chain restriction. Note the scattered plasma cells that have more normal features (cytoplasmic basophilia, pale para- nuclear hof, clumped nuclear chromatin) than the majority plasmacytoid cells Figure 3.24 Castleman disease, plasma cell variant showing monotypic kappa light chain staining. Arrows show unstained lambda-expressing plasma cells that have more mature nuclear features than the kappa-positive cells Figure 3.25 Same biopsy as shown in Figure 3.24 stained for lambda light chain. Note that the few lambda-positive plasma cells show much darker staining than the majority kappa-positive cells in Figure 3.24 ■■■【11 】Measles Figure 3.26 Measles lymphadenopathy. Warthin- Finkeldey giant cells in paracortex of lymph node after measles vaccination Figure 3.27 Electron micrograph of Warthin-Finkeldey giant cell formed by the fusion of plasma cells in a case of measles lymphadenopathy ■■■【12】CMV Figure 3.28 Low-power view of cytomegalovirus (CMV)- infected lymph node showing follicular hyperplasia and an expanded zone of monocytoid B-cells (upper right) Figure 3.29 High-power view of cytomegalovirus (CMV)-infected lymph node. A cell at the centre shows a characteristic CMV inclusion. Many of the surrounding monocytoid B-cells show apoptosis and there are scattered polymorph leukocytes Figure 3.30 Immunohistochemical preparation using a polyclonal rabbit antiserum to cytomegalovirus (CMV). The CMV antigens stained are predominantly intracytoplasmic ■■■【13】EBV Figure 3.31 Infectious mononucleosis lymphadenopathy. Low-power view showing paracortical blast cell hyperpla- sia partially surrounding a reactive follicle Figure 3.32 Infectious mononucleosis lymphadenopathy. Paracortex showing blast hyperplasia; note multinucle- ated cell and apoptotic nuclei Figure 3.33 Infectious mononucleosis lymphadenopathy showing cells resembling Reed-Sternberg cells in the paracortex Figure 3.34 Infectious mononucleosis lymphadenopathy. Immunoperoxidase technique showing IgM+ B-cell blasts in the paracortex ■■■【14】Dermatopathic lymphadenopathy Figure 3.35 Dermatopathic lymphadenopathy. Axillary lymph node showing expanded pale-staining paracortex Figure 3.36 Dermatopathic lymphadenopathy. High- power view showing characteristic interdigitating reticu- lum cells with elongated grooved and twisted nuclei and abundant pale cytoplasm Figure 3.37 Dermatopathic lymphadenopathy. Plastic- embedded section showing the characteristic morphol- ogy of interdigitating reticulum cells Figure 3.38 Dermatopathic lymphadenopathy. Section stained for S100 protein showing the expanded network of interdigitating reticulum cells in the paracortex Figure 3.39 Dermatopathic lymphadenopathy, imprint cytology. The interdigitating reticulum cells have grooved nuclei and abundant pale-staining cytoplasm ■■■【15】Inflammatory pseudotumor Figure 3.40 Inflammatory pseudotumour of lymph node showing follicular hyperplasia to the right and the spindle cell pseudotumour proliferation to the left Figure 3.41 Higher power view of inflammatory pseudo- tumour showing a spindle cell proliferation of myofibro- blasts, histiocytes and blood vessels infiltrated by lymphocytes and plasma cells Figure 3.42 Immunoperoxidase stain of the same lymph node using a polyclonal rabbit antiserum to Treponema pallidum. Numerous spirochaetes are seen throughout the lymph node ■■■【16】IgG4 related disease Figure 3.43 Immunoglobulin G4 (IgG4)-related disease in lymph node; low-power view showing storiform fibrosis Figure 3.44 High-power view of immunoglobulin G4 (IgG4) disease demonstrating the plasmacytic infiltrate Figure 3.45 Immunoglobulin G4 (IgG4) disease immunoperoxidase stained for IgG highlighting the IgG-positive plasma cells Figure 3.46 This is the same field as in Figure 3.45 immunoperoxidase stained with an antibody specific for immunoglobulin G4 (IgG4). The ratio of IgG4- to IgG-stained plasma cells is greater than 40 per cent ■■■【17】Kikuchi disease Figure 3.47 Kikuchi disease. Lymph node showing partial loss of architecture with widespread apoptosis and necrosis Figure 3.48 Kikuchi disease. Blast cells with numerous apoptotic bodies in the background Figure 3.49 Kikuchi disease. An area of almost complete apoptosis and necrosis Figure 3.50 Kikuchi disease. High-power view showing blast cells and histiocytes with characteristic crescentic nuclei (arrow) Figure 3.51 Kikuchi disease. Section stained for CD68, showing histiocytes with crescentic nuclei (arrow) and phagocytosed apoptotic debris ■■■【18】SLE Figure 3.52 Systemic lupus erythematosus of lymph node showing a wedge-shaped area of subcapsular necrosis. The area of necrosis is less extensive than that usually seen in Kikuchi disease Figure 3.53 Higher power view of systemic lupus erythematosus of lymph node showing apoptosis and necrosis without polymorph infiltration ■■■【19】Drug induced lymphadenopathy Figure 3.54 Drug-induced lymphadenopathy, showing reactive follicles and expanded paracortex Figure 3.55 Drug-induced lymphadenopathy. Paracortex showing blast cell hyperplasia and eosinophil micro-abscesses Figure 3.56 Drug-induced lymphadenopathy. High-power view of paracortex showing blast cells and eosinophils ■■■【20】ALPS Figure 3.57 Low-power view of a node from a patient with autoimmune lymphoproliferative syndrome (ALPS) showing marked parafollicular hyperplasia Figure 3.58 Higher power view of autoimmune lympho- proliferative syndrome (ALPS) lymph node showing expansion of the paracortex by medium-sized blast cells and small lymphocytes Figure 3.59 Immunoperoxidase stain of autoimmune lymphoproliferative syndrome (ALPS) lymph node for CD20 showing several primary follicles Figure 3.60 Autoimmune lymphoproliferative syndrome (ALPS) lymph node stained for CD79a. In addition to the primary follicles, large numbers of plasma cells are seen in the paracortex Figure 3.61 Autoimmune lymphoproliferative syndrome (ALPS) lymph node immunostained for CD5 showing that the paracortical expansion is mainly a result of T-cells Figure 3.62 Autoimmune lymphoproliferative syndrome (ALPS) lymph node immunostained for CD4. There are relatively few CD4 cells present, presumably because of the increased number of CD4- CD8- T-cells Figure 3.63 Autoimmune lymphoproliferative syndrome (ALPS) lymph node immunostained for CD8. The number of CD8 T-cells is not unusual but it highlights the paucity of CD4 T-cells ■■■【21】Rosi dorfman disease Figure 3.64 Rosai-Dorfman disease. Lymph node show- ing marked sinus histiocytosis with compression of other lymph node compartments Figure 3.65 Rosai-Dorfman disease. Prominent sinus histiocytosis Figure 3.66 Rosai-Dorfman disease. Methyl green pyronin-stained section. The medullary cords contain many pyroninophilic plasma cells. Note the lymphophagocytic histiocytes in the sinuses (arrows) Figure 3.67 Rosai-Dorfman disease. High-power view showing lymphophagocytic histiocytes ■■■【22】Lipogranulomatous Figure 3.68 Lymph node from porta hepatis showing a lipogranulomatous reaction to lipid. Lipid vacuoles in the paracortex and sinuses are surrounded by histiocytes and giant cells Figure 3.69 Lymphangiogram effect, para-aortic lymph node. The lipid-rich contrast medium has evoked a lipogranulomatous reaction in the lymph node sinuses Figure 3.70 Lymphangiogram effect. High-power view showing histiocyte and giant cell reaction to the contrast medium Figure 3.71 Whipple disease. The sinuses of the lymph node are filled with foamy histiocytes surrounding lipid vacuoles Figure 3.72 Whipple disease. Periodic acid-Schiff-stained section showing large numbers of bacilli in foamy histiocytes ■■■【23】Vascular transformation Figure 3.73 Vascular transformation of sinuses. The sinuses shown are filled with a meshwork of endothelial cell-lined vascular spaces ■■■【24】Suppurative granulomatous Figure 3.74 Cat scratch disease. Lymph node showing serpiginous areas of necrosis surrounded by palisaded epithelioid histiocytes Figure 3.75 Cat scratch disease. High-power view showing palisaded epithelioid histiocytes around an area of necrosis. Some of the nuclear debris at the centre of the area of necrosis is from polymorph leukocytes ■■■【25】Epithelioid granulomatous Figure 3.76 Tuberculous lymph node showing necrotizing epithelioid cell/giant cell granulomas. Note the tendency of the granulomas to coalesce Figure 3.77 Tuberculous lymph node showing caseating granulomas containing Langhans-type giant cells Figure 3.78 Bacille Calmette-Guérin (BCG)-infected lymph node from an immunocompetent patient showing a well-defined necrotizing granuloma Figure 3.79 Abdominal lymph node from a patient with Crohn's disease showing two granulomas Figure 3.80 Sarcoidosis of lymph node. The granulomas tend to remain discrete and to undergo progressive fibrosis Figure 3.81 Sarcoidosis of lymph node showing well- defined non-necrotizing epithelioid cell granulomas undergoing early sclerosis Figure 3.82 Sarcoidosis of lymph node showing an aster- oid body in a giant cell Figure 3.83 Lymph node from a patient with schisto- somiasis. There is marked capsular fibrosis with several granulomas surrounding schistosome ova Figure 3.84 Leishmaniasis of lymph node. Organisms are visible in the cytoplasm of the histiocytes Figure 3.85 Leishmaniasis of lymph node, Giemsa stain. The organisms are seen more easily with this stain than with haematoxylin and eosin Figure 3.86 Lepromatous leprosy. Foamy histiocytes (lepra cells) fill the paracortex of the node Figure 3.87 Lepromatous leprosy. High-power view of lepra cells Figure 3.88 Lepromatous leprosy. Stain for acid-fast bacilli shows large numbers of leprosy bacilli in lepra cells Figure 3.89 Bacille Calmette-Guérin (BCG)-infected lymph node from an immunosuppressed patient showing an area of necrosis surrounded by plump histiocytes Figure 3.90 Bacille Calmette-Guérin (BCG)-infected lymph node from an immunosuppressed patient stained by the Ziehl-Neelsen method. Large numbers of acid-fast bacilli fill the plump histiocytes Figure 3.91 Mycobacterium avium-intracellulare infection in an immunosuppressed patient. Sheets of pale-staining histiocytes replace the lymph node Figure 3.92 Mycobacterium avium-intracellulare infection. Ziehl-Neelsen-stained section, showing histiocytes filled with acid-fast bacilli ■■■【26】Impaired immune response Figure 3.93 Histoplasmosis. Clusters of yeasts are seen within the cytoplasm of histiocytes (arrow) Figure 3.94 Histoplasmosis. Grocott stain highlights the intracellular organisms Figure 3.95 Lymph node from a patient with onchocerciasis. There is fibrosis of the capsule and a microfilaria is seen in the subcapsular sinus (arrow). Since the organism was alive at the time of biopsy, it has not excited a granulomatous reaction ■■■【27】Foreign body Figure 3.96 Silicone lymphadenopathy. This paracortical giant cell reaction is to particulate silicone from a joint prosthesis Figure 3.97 Silicone lymphadenopathy. High-power view showing asteroid bodies and refractile silicone particles in the giant cells Figure 3.98 Enlarged groin lymph node from a patient with both hip and knee prostheses demonstrating numer- ous histiocytes in the paracortex Figure 3.99 High-power view of the lymph node in Figure 3.98 from a patient with both hip and knee prostheses demonstrating fragments of metal material in histiocytes Figure 3.100 Tattoo pigment in a hyperplastic lymph node. The pigment is mainly distributed in the paracortex Figure 3.101 Tattoo pigment viewed in polarized light showing multiple colours