Atlas of Spleen Pathology

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Dennis P. O’Malley, M.D.
Clarient Inc./GE Healthcare
Aliso Viejo
California
USA
Adjunct Associate Professor
Department of Hematopathology
M.D. Anderson Cancer Center/
University of Texas
Houston
Texas
USA

ISBN 978-1-4614-4671-2 ISBN 978-1-4614-4672-9 (eBook)

DOI 10.1007/978-1-4614-4672-9
Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2012948389

© Springer Science+Business Media New York 2013

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As with all of my works, I would like to dedicate this work to my wife, Karene. It is
through her love and support that I accomplish anything.
Preface

The spleen has always been mysterious in the history of medicine. It has had several characters
ascribed to it as a seat of emotions, or even as a site of pumping blood. However, in modern
medicine, the spleen, while well understood, still leads to diagnostic challenges. This is likely
due to its relative rarity as a diagnostic specimen, and the unusual combinations of pathology
that can occur. However, when considered in its component parts, splenic pathology can be
relatively straightforward and understood as an interesting mix of physiologic, anatomic, and
pathologic components. It is my hope that the images in this atlas, along with their descrip-
tions, will help bring some understanding and appreciation to this “organ of mystery.”

vii
Acknowledgment

I would like to acknowledge Attilio Orazi, Richard Neiman, Thomas Dutcher, and Peter Banks,
who nurtured my interest in hematopathology, and in splenic pathology, specifically. My spe-
cial thanks to the many pathologists who have shared gross images of splenic pathology; with-
out their help this atlas would be far less illustrative. Finally, I would like to thank all of my
colleagues for their help, insights, and support during the production of this book.

ix
Contents

1 Normal Morphologic and Immunohistochemical Findings and Hyperplasias

1.1 Anatomy and Normal Histology ........................................................................ 2
1.2 Hyperplasias ....................................................................................................... 6
1.3 Normal Immunohistochemistry ......................................................................... 7
2 Congenital Malformations and Abnormalities of Spleen Location
and Histology
2.1 Accessory Spleen ............................................................................................... 12
2.2 Intrapancreatic Spleen ........................................................................................ 13
2.3 Polysplenia ......................................................................................................... 13
2.4 Splenosis ............................................................................................................ 14
2.5 Splenogonadal Fusion ........................................................................................ 14
2.6 Other Findings.................................................................................................... 15
3 Lymphoid Neoplasms
3.1 Splenic Marginal Zone Lymphoma .................................................................... 18
3.2 Chronic Lymphocytic Leukemia ........................................................................ 23
3.3 Lymphoplasmacytic Lymphoma ........................................................................ 26
3.4 Follicular Lymphoma ......................................................................................... 27
3.5 Mantle Cell Lymphoma...................................................................................... 30
3.6 Plasma Cell Myeloma ........................................................................................ 32
3.7 Hairy Cell Leukemia .......................................................................................... 33
3.8 Hairy Cell Leukemia-Variant ............................................................................. 37
3.9 Splenic Diffuse Red Pulp Small B-Cell Lymphoma .......................................... 38
3.10 Prolymphocytic Leukemia ................................................................................. 39
3.11 Lymphoblastic Leukemia/Lymphoma ................................................................ 40
3.12 Hepatosplenic T-cell Lymphoma ....................................................................... 40
3.13 T-cell Large Granular Lymphocytic Leukemia .................................................. 43
3.14 Other T-cell Lymphomas .................................................................................... 46
3.15 Diffuse Large B-cell Lymphomas ...................................................................... 49
3.16 Hodgkin Lymphoma........................................................................................... 55
4 Myeloid and Related Disorders
4.1 Extramedullary Hematopoiesis .......................................................................... 60
4.2 Myeloid Sarcoma/Acute Myeloid Leukemia ..................................................... 61
4.3 Myeloproliferative Neoplasms ........................................................................... 64
4.4 Myelodysplastic Syndrome and Myelodysplastic/
Myeloproliferative Disorders ............................................................................... 69
4.5 Mastocytosis ....................................................................................................... 71
4.6 Histiocytic Sarcoma ........................................................................................... 73
5 Nonhematopoietic Lesions Including Vascular
5.1 Cysts ................................................................................................................... 76
5.2 Hamartoma ......................................................................................................... 78
5.3 Inflammatory Pseudotumor ................................................................................ 83

xi
xii Contents

5.4 Follicular Dendritic Cell Tumor ......................................................................... 84

5.5 Other Stromal Tumors ........................................................................................ 85
5.6 Splenic Artery Aneurysm................................................................................... 86
5.7 Benign Vascular Lesions .................................................................................... 87
5.8 Littoral Cell Angioma ........................................................................................ 92
5.9 Sclerosing Angiomatoid Nodular Transformation (SANT) ............................... 94
5.10 Vascular Tumors of Indeterminate and Malignant Behavior ............................. 96
5.11 Metastatic Tumors .............................................................................................. 99
Reference .................................................................................................................... 106
6 Reactive and Systemic Conditions
6.1 Rupture and Trauma ........................................................................................... 108
6.2 Infarction and Embolization ............................................................................... 109
6.3 Perisplenitis (Sugar-Coated Spleen)................................................................... 112
6.4 Congestive Splenomegaly .................................................................................. 113
6.5 Red Blood Cell Disorders .................................................................................. 114
6.6 Granulomas ........................................................................................................ 118
6.7 Langerhans Cell Histiocytosis............................................................................ 119
6.8 Storage Diseases................................................................................................. 120
6.9 Castleman Disease ............................................................................................. 127
6.10 Therapy Effects .................................................................................................. 128
6.11 Other Disorders .................................................................................................. 130
6.12 Hemophagocytic Syndrome ............................................................................... 132
6.13 Autoimmune Disorders ...................................................................................... 133
6.14 Immunodeficiency (Inherited and Acquired) ..................................................... 139
Reference .................................................................................................................... 142
7 Infections
7.1 Bacterial ............................................................................................................. 144
7.2 Mycobacteria ...................................................................................................... 145
7.3 Viruses ................................................................................................................ 147
7.4 Fungi .................................................................................................................. 151
7.5 Parasites and Protozoa........................................................................................ 155
Reference .................................................................................................................... 156
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
 Normal Morphologic and Immunohistochemical
Findings and Hyperplasias 1

Normal architecture is basic to an overall understanding of and also most closely mimicked by follicular lymphoma and
splenic pathology. In this chapter, normal components of splenic marginal zone lymphoma, respectively. Other more
spleen are illustrated. These include normal structures such rare hyperplasias include proliferations of T cells and immu-
as red and white pulp, stromal elements, and vascular com- noblasts. Finally, the immunohistochemical architecture of
ponents. In addition, hyperplasias of splenic components are the spleen is richly illustrated. This is particularly important
illustrated. These are important, as the differential diagnosis in the evaluation of splenic lesions, as understanding of nor-
of many splenic lesions and lymphomas are benign prolifera- mal patterns of staining must precede the evaluation of stains
tions of the same compartments. Follicular hyperplasia and in pathologic processes. A combination of histologic, immu-
marginal zone hyperplasia are most commonly encountered nohistochemical, and gross images is presented.

D.P. O’Malley, Atlas of Spleen Pathology, Atlas of Anatomic Pathology, 1

DOI 10.1007/978-1-4614-4672-9_1, © Springer Science+Business Media New York 2013
2 1 Normal Morphologic and Immunohistochemical Findings and Hyperplasias

1.1 Anatomy and Normal Histology

Fig. 1.3 Normal spleen parenchyma. A higher magnification high-

lighting the features of an individual white pulp nodule. This is com-
posed of a reactive germinal center with mantle zone and marginal
zone. Note that there is an adjacent splenic arteriole. White pulp nod-
ules are analogous to “buds” whereas the arterioles are analogous to
“branches.” The red pulp in this image shows typical features with some
patent sinuses and more solid-appearing cords

Fig. 1.1 A radiograph of the lower thoracic and abdominal cavity. The
spleen is present in the middle left, beneath the ribs. The spleen is seen
as a round or bean-shaped organ. It lies adjacent to the stomach and
lateral to the pancreas

Fig. 1.2 Normal spleen parenchyma. An intermediate magnification of Fig. 1.4 Normal spleen red and white pulp. This low magnification
normal spleen parenchyma. In this image, there are appropriate numbers of image of spleen shows a typical normal proportion of red pulp (RP) to
germinal centers and white pulp admixed with red pulp. The white pulp white pulp (WP). In general, the ratio of RP:WP is about 3–4:1, as in
nodules are in their usual functional form, showing a tripartite arrangement, this case
with a germinal center (pale), a thin mantle zone (dark), and a pale outer
marginal zone. Some large caliber vessels (arterioles) are also present. Red
pulp shows some patent sinuses, with some circulating red blood cells
1.1 Anatomy and Normal Histology 3

Fig. 1.5 Red pulp. The splenic red pulp is composed of predominantly Fig. 1.8 Spleen capsule. Another example of normal spleen capsule
splenic sinuses and splenic cords. Sinuses are lined by specialized (upper). The capsule is 50–100 microns thick. The presence of
endothelial cells (eg, splenic littoral cells). The intervening spaces are significant cellular infiltrates can indicate pathology
splenic cords. They contain stromal elements including splenic mac-
rophages and some occasional lymphocytes

Fig. 1.9 Fibrous trabeculae. Bands of fibrous tissue, contiguous with

the capsule, are present in the central portions of the spleen. There are
Fig. 1.6 Red pulp. Red pulp is a hypoxic environment. Red blood cells approximately the same thickness as the capsule and provide a frame-
enter into the splenic cords and then must traverse the walls of the work for vascular and stromal elements in the spleen
sinuses to return to the circulation. If red cells are not deformable, they
will be destroyed by splenic macrophages

Fig. 1.7 Spleen capsule. In this microscopic image, the spleen capsule Fig. 1.10 Splenic artery, elastin stain. Elastin stain of normal splenic
is present (lower). It is typically paucicellular with only rare, unremark- artery. Note the staining within the artery wall and the notable lack of
able spindle-shaped stromal cells present staining within the splenic red pulp. Elastic fibers are not a normal part
of the splenic red pulp architecture
4 1 Normal Morphologic and Immunohistochemical Findings and Hyperplasias

Fig. 1.11 Splenic sinus, Grocott’s methenamine silver (GMS) stain. In Fig. 1.14 Hyaline deposition, germinal center. In this example of a
this GMS stain, the “ring fibers” that wrap the endothelial sinus lining cells germinal center, there is hyalinized protein (glassy, pink material) pres-
are highlighted. These are akin to hoops around the staves of barrel ent in the central portion of the germinal center. In some circumstances,
this represents immunoglobulin protein deposition; however, in other
cases, its exact nature is not known. It is a benign finding and not
specific for any diagnosis

Fig. 1.12 Vessels, splenic hilum. This low magnification image shows
vessels in the splenic hilum. Hilar vessels include large caliber arteries and
veins, as well as lymphatics. The arteries merge together to form the
splenic artery. Only very limited lymphatics are present in the spleen.
They are seen only in the adventitial regions of the largest vessels penetrat-
ing the spleen. Normal splenic parenchyma does not have lymphatics Fig. 1.15 White pulp nodule. This example shows the component of a
typical white pulp nodule. The usual follicles have a three-layer struc-
ture. The central portion is the germinal center (eg, secondary follicle).
The second layer is the mantle zone, composed of small, dark-blue,
slightly irregular lymphocytes. Finally, the third layer is the marginal
zone, composed of mostly small lymphocytes with increased amounts
of pale cytoplasm

Fig. 1.13 Red pulp sinuses. In this example, the splenic sinuses are
patent. Cells within the sinus would likely be seen in the peripheral
blood circulation. Other more solid-appearing areas are cords
1.1 Anatomy and Normal Histology 5

Fig. 1.16 White pulp nodule. As in the previous example, this white Fig. 1.18 Periarteriolar lymphoid sheath. A longitudinal section of a
pulp nodule is composed of three layers: germinal center, mantle zone, splenic arteriole with surrounding lymphoid sheath. These lymphoid
and marginal zone. Note at the periphery is an arteriole in cross section, cells are predominantly T cells, although there are also occasional
which continues into the spleen and is surrounded by the periarteriolar admixed B cells
lymphoid sheath (PALS) region

Fig. 1.17 White pulp nodule, primary follicle. In the unreacted spleen, Fig. 1.19 Pediatric spleen. Although not instantly apparent, this is a
germinal centers have not been formed. In these cases, the white pulp spleen from a 1-year-old patient. The subtle morphologic clue lies in
nodules have only two layers, the “mantle cell” core and the marginal the perisplenic adipose tissue. There are lipoblasts present, which per-
zone. These are “primordial” follicles or primary follicles, which have sist for a short time after birth (2–5 years)
not undergone a germinal center reaction
6 1 Normal Morphologic and Immunohistochemical Findings and Hyperplasias

1.2 Hyperplasias

Fig. 1.22 Nodular lymphoid hyperplasia. Nodular (follicular) lym-

phoid hyperplasia is a rare finding in spleens. It may be grossly visible
Fig. 1.20 Follicular hyperplasia. This gross image of an enlarged as an enlarged white pulp nodule, mimicking focal involvement by a
spleen shows an increase in accentuation of white pulp components lymphoid process or perhaps a granulomatous or inflammatory process.
corresponding to follicular hyperplasia. The accentuation of white pulp Histologic examination reveals a coalescence of benign reactive germi-
nodules is the spleen is said to impart a miliary appearance, which nal centers. These aggregate into nodules, thereby mimicking neoplas-
refers to the small white nodules appearing like millet seeds (small tic processes. However, the morphologic and immunohistochemical
grains). Compared to a normal spleen, these white pulp nodules are features of the individual follicles and cells are compatible with a reac-
increased in size and density. The findings are not specific, and could tive process
look similar to a lymphoma with involvement of the white pulp. (Image
courtesy of D. Farhi, Atlanta, GA, USA)

Fig. 1.21 Follicular hyperplasia. In this low magnification image, Fig. 1.23 Marginal zone hyperplasia. Hyperplasia of the splenic mar-
there is an increase in the proportion of white pulp compared to red ginal zone has been arbitrarily defined as a thickening of the marginal
pulp, which is seen in follicular hyperplasia. The causes of follicular zone (third) layer of more than 10 cells. This case is at the borderline of
hyperplasia are broad, and in general are related to immune activation marginal zone hyperplasia, with possibly 10 or fewer cells in the third
layer. The remaining features are of a typical reactive follicle
1.3 Normal Immunohistochemistry 7

1.3 Normal Immunohistochemistry

Fig. 1.24 Marginal zone hyperplasia. In this case, there is clear expan-
sion of the outer (pale) layer of the follicular structure. There are more
than 10 cells in this layer, which constitutes marginal zone hyperplasia. Fig. 1.26 CD3, normal spleen. The distribution of T cells in the nor-
The cytologic composition is predominantly small and intermediate mal spleen includes cells within the germinal center, some cells scat-
sized lymphocytes, with round nuclei and increased amounts of pale tered in the mantle and marginal zones, many in the periarteriolar
cytoplasm, imparting their marginal zone appearance. They are distin- lymphoid sheath, and scattered throughout the white pulp
guished from the “mantle type” cells in the center that are smaller, have
dark blue nuclei, and almost no cytoplasm

Fig. 1.25 Primary follicle hyperplasia. In this example, there is a pri- Fig. 1.27 CD3, normal spleen, periarteriolar lymphoid sheath. This
mary follicle present. Hyperplasia of primary follicle is a rare finding. CD3 stain highlights CD3-positive T-cells in the periarteriolar lym-
It is characterized by an overall increase in white pulp nodules com- phoid sheath (PALS) region. In the splenic white pulp, this is a normal
posed of B cells without germinal center formation. The circumstances distribution of T cells adjacent to arterioles
of primary follicle hyperplasia are most often seen in early immuno-
logic responses, in pediatric spleens and in association with suppression
of the normal immune response, such as with steroid therapy