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Handbook ol
Hematologic
Pathology
DIAGNOSTIC PATHOLOGY
1. Diagnostic Neuropathology, Harry V. Vinters, Michael A. Farrell, Paul S.

Mischel, and Karl H. Anders
2. Handbook of Hematologic Pathology, edited by Harold R. Schumacher,

William A. Rock, Jr., and Sanford A. Stass
ADDITIONAL VOLUMES IN PREPARATION

Handbook ol
Hematologic
Pathology
edited by
HAROLD R. SCHUMACHER
University of Cincinnati Medical Center
Cincinnati, Ohio
WILLIAM A. ROCK, JR.

University of Mississippi Medical Center
Jackson, Mississippi
SANFORD A. STASS
University of Maryland School of Medicine
Baltimore, Maryland
t::;:\ Taylor & Francis

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In loving memory of my parents, Catherine and Philip
Harold R. Schumacher
To Vannie, William, and Megan,

whose patience and acceptance of the time to write these pages
will forever be appreciated.
William A. Rock, Jr.
To my wife, Ann, and in loving memory of my father, Morris

Sanford A. Stass
Preface
This book should capture the interest of a large audience engaged in or dependent on laboratory
hematology, including medical technologists, medical students, hematologists, and hematopa-
thologists. It should be helpful to those preparing for boards related to hematology. In addition,
it offers a source of rapid review for individuals who have been working outside hematology
for a while and who wish to return to the field with up-to-date knowledge. Furthermore, the
book provides an expeditious source of cross-training that will be especially valuable to medi-
cal technologists who are required to be competent in various areas of the laboratory.
This book was written by authors who apply every day what they write about in their
chapters. Theory is fine and needs to be understood, but learning and knowing how to apply
the information to the patient's situation is one of the major goals of this text. This goal is
achieved through direct discussion of the issues and theory and application of the information
by using case histories. The approach is not to solve all the reader's problems, but rather to
show how to gather information about a problem and how to deal with it. Individual variations
in approaches are expected, since everyone will have different experiences and new methods
and technologies become available every day. What this book is designed to achieve is to help
the reader develop a method to look at a problem and to think about diagnosing and fixing
what can be fixed.
We have stressed certain basic approaches or themes throughout the book that should
appeal to a wide segment of the medical community. These include the simplicity of style,
ease of readability, current information, ready application of the information to a working
laboratory, and other practical applications. To further emphasize applications some case stud-
ies are offered at the end of each chapter to allow the reader to become involved in the
pragmatic use of the new knowledge acquired.
This book reflects the varied backgrounds of the editors. Dr. Schumacher began his career
in clinical hematology/oncology with a special interest in leukemias and ultimately migrated
to laboratory hematology. Dr. Rock began his career in morphologic atherosclerosis and found
a home as a clinical pathologist and developing practical experience and knowledge in the
field of applied coagulation. Dr. Stass began his career in bone marrow pathology and the
study of hematology and malignancies and eventually emerged as a cancer center director. As
editors, we selected a group of authors who are experts in their fields. The editors thank them
for a job well done.
The editors have directed their efforts toward the diagnosis and management of hematolog-
ical problems, utilizing practical, current, and relevant laboratory investigative procedures.
However, we have also emphasized pertinent clinical information in those areas where such
knowledge is a necessary adjunct to diagnosis.
v
vi Preface
The book further directs medical technologists, hematopathologists, and hematologists on

how to utilize blood, plasma, serum, instrumentation, bone marrow, lymph nodes, and splenic
tissue to establish a diagnosis.
Finally, the book emphasizes practical technical information to aid in the operation of an
efficient hematology laboratory involved in hematological procedures. The editors anticipate
the reader will enjoy a book directed toward a practical and useful source of laboratory hemato-
logical information.
Harold R. Schumacher
Sanford A. Stass
Acknowledgments
We are indebted to a number of people who through their efforts, support, and cooperation
made this book possible.
Harold R. Schumacher would like to give a very special thanks to our secretaries Pat
Hathaway and Roland Randolph, and Pauline Harris, administrative coordinator, who commu-
nicated with many of the contributors, the editor, and the staff.
Special thanks to our fellows in hematopathology, Fermina Mazzella and Carmelita Al-
vares, who helped us read and edit many of the chapters.
Further thanks to the pathology residents at our institutions who provided new information
and procedures that were important to our presenting a timely content.
In addition, our gratitude is extended to Dr. Paul Steele, who gave advice and counsel in
molecular hematology; Dr. Ruth Blough, in cytogenetics; and Dr. Paul Hurtubise, in flow
cytometric analysis.
William A. Rock, Jr., would like to thank the medical technologists (particularly Dan
Haun and Pam Moore) in the Hematology and Coagulation Laboratories at Charity Hospital,
New Orleans, Louisiana, and University Hospital, Jackson, Mississippi, who were eager to
push the envelope in developing new procedures in coagulation and assuring that they worked
consistently. He is also grateful to the Pathology Residents at Charity Hospital, New Orleans,
Louisiana, and University Hospital, Jackson, Mississippi, who struggled tirelessly to implement
the new approaches and procedures for bleeding and clotting problems.
Finally, Dr. Rock thanks Dr. Alain Marengo-Rowe, whose encouragement and conviction
were an inspiration to aggressively assault the coagulation problem, to learn about it, and to
struggle with the difficult cases, as well as Dr. Frederick G. Schechter, who first opened for
me the door to the direct laboratory application of coagulation theory to the more complex
patient coagulophathies; Dr. Douglas Triplett, whose thoughtful support was an inspiration to
continue writing, and Dr. Jack Perry Strong, for without his confidence and trust none of this
would have happened.
Lastly, a very special thanks to Elizabeth Curione, production editor at Marcel Dekker,
Inc., for her tenacity of purpose and encouragement. We all enjoyed working with her.
vii
Contents
Preface v
Acknowledgments vii
Contributors xiii
Peripheral Blood and Bone Marrow 1

Fermina Maria Mazzella and Gerardo Perrotta
2 Benign Lymph Node Lesions 27

Robert J. Hartsock
3 Pathology of the Spleen 53

Hernani D. Cualing
4 The Non-Hodgkin' s Lymphomas and Plasma Cell Dyscrasias 75

Lynne V. Abruzzo and L. Jeffrey Medeiros
5 Hodgkin's Disease 121

Lynne V. Abruzzo, L. Jeffrey Medeiros, and Kojo S.J. Elenitoba-Johnson
6 Histiocytosis and Lipid Storage Diseases 145

Salwa Shabbir Sheikh and David F. Garvin
7 Benign Disorders of Leukocytes 171

Gene L. Gulati, Zoran Gatalica, and Bong H. Hyun
8 Acute Leukemia and Myelodysplastic Syndromes 193

Mark D. Brissette and James D. Cotelingam
9 Chronic Leukemias 223

Scott J. Graham and James D. Cotelingam
10 Myeloproliferative Disorders 257

Powers Peterson
11 Anemia: Approach to Diagnosis 275

William F. Baker, Jr.
ix
X Contents
12 Iron Deficiency Anemia 293

Donald P. Skoog and James R. Newland
13 Megaloblastic Anemias 309

LoAnn C. Peterson
14 Anemias of Chronic Disorders and Nonhemolytic Normochromic,

Normocytic Anemias 325
Robert T. Means, Jr.
15 Sideroblastic Anemia and Porphyrias 341

Lawrence Kass
16 Anemias of Bone Marrow Failure 357

17 Hemoglobinopathies and Thalassemias 369

Donald L. Rucknagel
18 Hemolytic Anemias: General Considerations 395

19 Hemolytic Anemia Associated with Red Cell Membrane Defects 405

John C. Winkelmann
20 Abnormal Red Cell Metabolism 425

Abdus Saleem
21 Immune Hemolytic Anemias 435

Joseph P. Yoe and Robert A. Sacher
22 Carbon Monoxide Poisoning, Methemoglobinemia, and Sulfhemoglobinemia 455

Ronald L. Nagel
23 Practical Approach to Molecular Biology in Hematopathology 475

Anwar Mikhael and Harold R. Schumacher
24 Coagulation Theory, Principles, and Concepts 493

Robert F. Baugh
25 Laboratory Instrumentation, Reagents, Methods, and Patient Sample as Variables

in Coagulation 521
James W. Cook and William A. Rock, Jr.
26 The Decision Process in the Laboratory Diagnosis and Management of

Bleeding and Clotting Disorders 547
Contents xi
27 Concepts of Replacement Therapy: Blood Components, Blood Derivatives,

and Medications 559
Francis R. Rodwig, Jr.
28 Hereditary Cause for Plasma Clotting Bleeding 579

Aubrey A . Lurie
29 Congenital Platelet Dysfunction and von Willebrand Disease 591

Jonathan L. Miller
30 Acquired Bleeding Disorders Associated with Disease and Medications 611

William A. Rock, Jr., and Sue D. Walker
31 Acquired Bleeding Disorders Associated with the Character of the Surgery 655
William A. Rock, Jr., and Robert F. Baugh
32 Anticoagulation 691
Louis M. Fink, Nicole A. Massoll, and Alex A . Pappas
33 Hereditary and Acquired Causes of a Hypercoagulable State 717

Robert B. Fairweather
34 Quality Control and Quality Assurance in Hematology 739

Bradley E. Copeland
Index 751
Contributors
Lynne V. Abruzzo, M.D., Ph.D. Department of Pathology, University of Texas M.D. Ander-
son Cancer Center, Houston, Texas
William F. Baker, Jr., M.D., F.A.C.P. Department of Medicine, U.C.L.A. Center for Health
Sciences, Los Angeles, California
Robert F. Baugh, Ph.D. Department of Research, Medtronic Blood Management, Parker,

Colorado
Mark D. Brissette, M.D. Division of Hematology/Flow Cytometry, Department of Pathol-

ogy, Madigan Army Medical Center, Tacoma, Washington
Bradley E. Copeland, M.D.* Department of Pathology and Laboratory Medicine, University

of Cincinnati Medical Center, Cincinnati, Ohio
James W. Cook, M.D. Departments of Pathology and Family Medicine, University of Mis-
sissippi Medical Center, Jackson, Mississippi
James D. Cotelingam, M.D. Department of Pathology, Louisiana State University Medical

Center, Shreveport, Louisiana
Hernani D. Cualing, M.D. Department of Pathology and Laboratory Medicine, University

of Cincinnati Medical Center, Cincinnati, Ohio
Kojo S. J. Elenitoba-Johnson, M.D. Department of Pathology, University of Utah Health

Sciences Center, Salt Lake City, Utah
Robert B. Fairweather, M.D., Ph.D. Department of Pathology, Dartmouth Hitchcock Medi-

cal Center, Lebanon, New Hampshire
Louis M. Fink, M.D. Department of Pathology, University of Arkansas for Medical Sciences
and Little Rock Veterans Administration Medical Center, Little Rock, Arkansas
*Former Chairman of the Commission on World Standards, World Association of Pathologists
xiii
xiv Contributors
David F. Garvin, M.D. Department of Pathology, Georgetown University Medical Center,

Washington, D.C.
Zoran Gatalica, M.D., D.Sc. Departments of Pathology and Hematology, Jefferson Medical
College, Thomas Jefferson University, Philadelphia, Pennsylvania
Scott J. Graham, M.D. Department of Pathology, Naval Medical Center, Portsmouth,

Virginia
Gene L. Gulati, Ph.D., SH (ASCP), DLM Department of Pathology, Anatomy, and Cell
Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
Robert J. Hartsock, M.D. Department of Laboratory Medicine, Allegheny General Hospital,

Pittsburgh, Pennsylvania
Bong H. Hyun, M.D., D.Sc. Department of Laboratory Medicine, Ajou University School
of Medicine, Suwon City, Korea, and Jefferson Medical College, Thomas Jefferson University,
Philadelphia, Pennsylvania
Lawrence Kass, M.S., M.D. Department of Pathology and Medicine, Case Western Reserve
University School of Medicine, and Metro Health Medicine Center, Cleveland, Ohio
Aubrey A. Lurie, M.D. Department of Pathology, Louisiana State University Medical Cen-
ter, and Department of Pathology and Laboratory Medicine Service, Overton Brooks VA Medi-
cal Center, Shreveport, Louisiana
Nicole A. Masson, M.D. Department of Pathology, University of Arkansas for Medical Sci-
ences, Little Rock, Arkansas
Fermina Maria Mazzella, M.D. Department of Pathology and Laboratory Medicine, The
Guthrie Clinic, Sayre, Pennsylvania
Robert T. Means, Jr., M.D. Hematology-Oncology Division, Department of Medicine,

Medical University of South Carolina and R. H. Johnson VA Medical Center, Charleston,
South Carolina
L. Jeffrey Medeiros, M.D. Department of Pathology, University of Texas M.D. Anderson

Cancer Center, Houston, Texas
Anwar Mikhael, M.D., Ph.D. Department of Pathology and Laboratory Medicine, Univer-
sity of Cincinnati Medical Center, Cincinnati, Ohio
Jonathan L. Miller, M.D., Ph.D. Department of Pathology, State University of New York
Health Science Center at Syracuse, Syracuse, New York
Ronald L. Nagel, M.D. Albert Einstein College of Medicine, Bronx, New York
James R. Newland, M.D. Department of Pathology and Microbiology, University of Ne-

braska College of Medicine, Omaha, Nebraska
Contributors XV
Alex A. Pappas, M.D. Departments of Pathology and Laboratory Medicine, University of

Arkansas for Medical Sciences, Little Rock, Arkansas
Gerardo Perrotta, M.P.A., M.T.(A.S.C.P.)S.H. Department of Pathology and Laboratory

Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio
LoAnn C. Peterson, M.D. Department of Pathology, Northwestern University Medical Cen-

ter, Chicago, Illinois
Powers Peterson, M.D. Department of Pathology, Sentara Norfolk General Hospital, Nor-
folk, Virginia
William A. Rock, Jr., M.D. Division of Clinical Pathology, Department of Pathology, Uni-
versity of Mississippi Medical Center, Jackson, Mississippi
Francis R. Rodwig, Jr., M.D., M.P.H. Blood Bank, Ochsner Medical Institutions, New
Orleans, Louisiana
Donald L. Rucknagel, M.D., Ph.D. Department of Pediatrics and Internal Medicine, Univer-
sity of Cincinnati College of Medicine, and Hemoglobin Diagnostic Laboratory, Cincinnati
Comprehensive Sickle Cell Center, Children's Hospital Medical Center, Cincinnati, Ohio
Ronald A. Sacher, M.D., F.R.C.P.C. Department of Laboratory Medicine, Georgetown Uni-

versity Medical Center, Washington, D.C.
Abdus Saleem, M.D. Department of Pathology, Baylor College of Medicine, Houston, Texas
Harold R. Schumacher, M.D. Department of Pathology and Laboratory Medicine, Univer-

sity of Cincinnati Medical Center, Cincinnati, Ohio
Salwa Shabbir Sheikh, M.D. Department of Pathology, Georgetown University Medical

Center, Washington, D.C.
Donald P. Skoog, M.D. Department of Pathology and Microbiology, University of Nebraska

College of Medicine, Omaha, Nebraska
Sanford A. Stass, M.D. Department of Pathology and Program in Oncology, University of

Maryland School of Medicine, Baltimore, Maryland
Sue D. Walker, M.D. Department of Pathology, Hattiesburg Clinic, Hattiesburg, Mississippi
John C. Winkelmann, M.D., F.A.C.P. Division of Hematology-Oncology, University of

Cincinnati College of Medicine, Cincinnati, Ohio
Joseph P. Yoe, M.D. Division of Hematology/Oncology, Department of Medicine, North

General Hospital, New York, New York
1
Peripheral Blood and Bone Marrow
Fermina Maria Mazzella

The Guthrie Clinic, Sayre, Pennsylvania
Gerardo Perrotta
University of Cincinnati Medical Center, Cincinnati, Ohio
I. PERIPHERAL BLOOD
A properly prepared and stained peripheral blood smear remains an essential component in the
practice of laboratory hematology. Although many automated hematology instruments have
lessened the need for peripheral blood smear (PBS) review, none has been able to totally
replace human evaluation. The slide, then, augments the quantitative analysis of sophisticated
instruments with the qualitative assessment made by the pathologist ancl!or technologist in
cases requiring interpretive and diagnostic findings not currently detected by automated instru-
ments.
A. Preparation of Smear
There are two common methods for preparation of peripheral blood films:
1. Preparation on glass slides (push or spinner)

2. Preparation on coverslips
The glass slide method is shown in Fig. 1. Blood from a fingerstick is preferable, although
ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood is used more frequently. Glass
slides have the advantages of
1. Ease of handling and labeling

2. Ease of smear production and staining
3. Lack of fragility- easy to store and transport
The major disadvantage of a glass slide is the irregular distribution of cells, which may cause
difficulty in evaluating platelets and leukocytes. Slides made from a fingerstick may invalidate
platelet estimates, in that their distribution is characteristically clumped or clustered.
The coverslip technique is more difficult to master. A small drop of either EDTA-anticoag-
ulated blood or blood from a fingerstick is placed in the center of a coverslip. A second
1
2 Mazzella and Perrotta
Figure 1 Glass slide method for preparation of peripheral blood smear: A, slide with small drop of
blood; B, spreader slide is pulled back over drop of blood; C, spreader slide is advanced in smooth
motion; D, completed slide. (From Schumacher et al., 1984.)
coverslip is placed over the one containing the drop. The blood spreads between the coverslip
by capillary action. Then the two coverslips are separated with a steady, firm, quick, gentle
pulling motion in appropriate directions (Fig. 2). The major advantage to this method is the
uniform distribution of platelets and leukocytes over the entire coverslip. The disadvantages,
as mentioned previously, are mainly in the handling and labeling.
Automated slide-smearing processors have been developed for producing uniform smears.
These instruments usually spread cells either by mechanical means or by centrifugation. Smears
prepared manually by an experienced technologist are preferred over those made by a mechani-
cal slide maker. The centrifugation method has the obvious disadvantage of being time con-
surning for preparation of routine slides.
Under special circumstances when body fluids other than blood are being examined, a
cytocentrifuge is necessary to concentrate the small numbers of cells to be identified. A mono-
layer of cells is concentrated on a small circular area of a glass slide.
In general, an acceptable blood smear will cover one-half to two-thirds of the glass slide,
with the feathered end producing a rainbowlike effect when held to the light.
B. Staining of Smear
Blood smears are usually stained with either Wright's or May-Grunwald-Giemsa stains, which
are modifications of the original Romanowsky techniques. These are polychrome stains, formu-
/
Figure 2 Coverslip method for preparing peripheral blood smears. Coverslips are pulled in directions
of arrows. (From Schumacher et al., 1984.)
lated from methylene blue and eosin, which color the cell constituents at the appropriate pH
of 6.4-6.8. Wright's stain uses sodium bicarbonate to convert methylene blue to the active
forms (methylene azures). Giemsa stains add acid biochromate-converted azure compounds.
Most Romanowsky stains are of no value when water is present in the alcohol, since neutral
dyes are precipitated from the solution. Acetone in the alcohol creates a similar problem. The
active forms of methylene blue are basic dyes which impart a violet-blue color to nucleic
acids and nucleoproteins. Eosin is an acidic compound which stains pink-orange-red the basic
components of the cell, such as hemoglobin and eosinophilic granules.
Although manual staining procedures are no longer used in most automated laboratories,
understanding of ideal staining conditions for manual methods enhances an appreciation of
evolving automated staining instruments. The slides or coverslip preparations may be fixed
with anhydrous methyl alcohol or air dried. For Wright's stain, the material on the glass surface
is covered with dye for 2-3 min. Then an equal volume of phosphate buffer is added and
mixed by blowing on the surface or drawing the mixture up and down gently in an eyedropper.
A greenish metallic sheen should appear on the surface of the stains, indicating optimal pH.
The buffer-stain mixture is incubated for approximately 3 min, but this time varies from batch
to batch of reagents. The smear is washed by adding drops of distilled water to the horizontal
slide or coverslip. This process allows the precipitated stain to float off the surface. The slide
is then washed vigorously, air dried, and mounted. Macroscopically, a good stain appears
salmon-pink. The nuclei of leukocytes appear purplish blue; erythrocytes stain pink. Eosino-
philic granules should be orange-red. There should be no background stain or debris in the
area between the cells.
Excessive blueness of the smear may be related to one of these factors:
1. Thick smear (due to high white blood cell count, protein abnormality, etc.)
2. Prolonged staining
3. Insufficient washing with buffer

4. Excessive alkalinity of stain, buffer, or water (pH >6.8)
Such blueness may be improved by decreasing the staining time or increasing the washing
time. Alternatively, less stain and more diluent may be used. If these alterations do not correct
the problem, the buffer may be too alkaline. A new mixture of buffer should be prepared.
If the whole stain is too red, the coloration is usually due to
1. Excessive acidity of the buffer, or water (pH <6.4)

2. Short staining time
3. Excessive washing
4. Very thin smears
To correct excessive acidity, it is usually necessary to use a fresh batch of stain and/or buffer.
Also, substituting alkaline tap water for distilled water in washing may be beneficial.
If nuclei, eosinophilic granules, and erythrocytes are pale, the washing time should be
decreased and the staining time should be increased.
Serum or precipitated stain between the cells is related to
1. Faulty washing
2. Unclean coverslip
3. Dust on the smear
4. Talc from gloves
These problems can be eliminated by holding the slide horizontally during washing, using
clean coverslips, and keeping smears clean during preparation and staining.
A number of commercially prepared stains are available. Most utilize a modified Wright-
Giemsa technique requiring much less time than the procedure described above. Some stains
are "quick" stains and can impart colors within 10 sec. In general, the results from these stains
are acceptable. Care must be exercised in keeping the stain and rinse solution clean.
The previously described techniques outline a manual method for staining slides and cov-
erslips with Wright stain. Modem, high-volume laboratories utilize automated slide stainers,
which can handle a large volume of slides. Some stainers convey separate slides face down
over a precision-formed flat area, where exact amounts of stain, buffer, and rinse are applied.
The solutions are delivered into a capillary space between the slide and the flat surface of the
instrument. After the first slide, this type of instrument can stain one slide per minute. Other
automated stainers use the dip method of staining and can handle up to 50 slides at one time.
These can be stained and dried in about 10 min.
Whatever method is used, the resulting stained slide appears pinkish-gray to the naked
eye. If not, they can be rinsed with methanol and restained, even after a long period of time
has elapsed.
After staining, the smear should be examined first under a low-power lens to determine
overall distribution of the cells. If this distribution is satisfactory, an ideal area is then selected
for evaluation (Fig. 3). A systematic approach should be used to evaluate every peripheral
smear. The order in which the elements are examined is inconsequential, provided that all
cellular constituents are included. Leukocytes are evaluated as to number, differential count,
and morphologic abnormalities. Platelets are evaluated as to number and abnormal morphol-
ogy. Erythrocytes are evaluated as to size, shape, color, and inclusions.
Figure 3 Peripheral blood smear: A, thick area with clumped RBCs and rouleaux; B, ideal area with
RBCs just touching; C, feather edge with cobblestone appearance. (From Schumacher et al., 1984.)
C. Morphology of Erythrocytes
The qualitative assessment must correlate with quantitative factors [red blood cell (RBC) count,
hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), red cell distribution
width (RDW)] and must explain flags generated by the automated cell-counting instruments.
It is very important to evaluate the size of RBCs on the peripheral smear, since size may
be the first clue to the cause of an anemia. The erythrocytes are macrocytic (large), normocytic
(normal), or microcytic (small) when compared to the nucleus of the mature lymphocyte.
Variation in size (anisocytosis) is estimated and recorded on a 0 to 4-plus scale or simply as
present or increased.
The presence of abnormally shaped cells such as teardrops, sickle cells, spur cells (long
irregular points), schistocytes (RBC fragments), and ovalocytes must be noted, since these cells
have diagnostic significance (Fig. 4). The degree of variation in shape (poikilocytosis) should
be evaluated and recorded on a 0 to 4-plus scale or as present or increased.
The intensity of color in erythrocytes is extremely important, since it can be used to
estimate the mean corpuscular hemoglobin concentration fairly accurately. Variation in color
(anisochromia) between erythrocytes may be associated with transfused blood or sideroblastic
anemia. Hypochromia, when present, should be scored 1 to 4-plus or present or increased.
Inclusions such as basophilic stippling (small, diffuse particles, composed of RNA), How-
ell-Jolly bodies (larger spherical particles, usually single, composed of DNA), precipitated
hemoglobin (HbC), and nucleated and parasitized RBCs are noted (Fig. 5). The number of
nucleated RBCs is usually expressed per 100 leukocytes in the differential count.
D. Platelets (Thrombocytes)
The qualitative assessment must correlate with quantitative factors [platelet count, mean plate-
let volume (MPV), and platelet distribution width (PDW)] and must explain flags generated
by the automated cell-counting systems.
The platelet count is estimated roughly by evaluating 10 oil-immersion fields, calculating
Figure 4 Teardrops in peripheral blood smear of patient with myelofibrosis. (From Schumacher et al.,
1984.)
Figure 5 Peripheral blood smear showing malaria inclusions (trophozoites, schizonts, and Schi.iffner' s
dots). (From Schumacher et al., 1984.)
an average number of platelets per field, and multiplying by 15,000. The platelets should be
evenly distributed on the slide when making such an evaluation. Platelets cluster on slides
prepared from fingersticks and render estimates difficult. No report should go out as "no plate-
lets seen" until the entire slide has been reviewed. The size and morphology of platelets may
vary in disease. Usually, platelets have a central granular area, granulomere, surrounded by a
hyalomere and measure 1-3 jlm in diameter. In disease they may become extremely large and
bizarre, as in myeloproliferative disorders. In some disorders the platelets may be quite small,
as in iron deficiency. All morphologic variants should be included in the report.
E. Leukocytes
The qualitative assessment must correlate with quantitative factors (WBC, relative and absolute
counts) and must resolve flags generated by the automated cell-counting system.
The leukocytes are evaluated as to number, type, and morphology. An estimate of the
white blood count is made by observing the number of leukocytes per high-power field. Leuko-
cytes are usually classified by an oil-immersion lens (SOx or lOOx). One hundred sequential
cells are counted (differential count), and a percentage is determined for each population of
cells. The absolute numbers of a particulate cell type are calculated by multiplying the total
leukocyte count by the percentage obtained in the differential count. It is as important to note
if certain types of cells are excessive (small lymphocytes, monocytes, granulocytes) or absent
(granulocytes) as it is to look for immature white cell elements. All of these morphologic
abnormalities have diagnostic significance: toxic granulation (large basophilic granules), hi-
lobed neutrophils, multisegmented neutrophils (over five lobes), Doble bodies (light blue bod-
ies of endoplasmic reticulum in the cytoplasm, Fig. 6), and degeneration and vacuolization of
the nucleus and cytoplasm. All such findings should be evaluated in light of the clinical picture
and other laboratory parameters.
Figure 6 Neutrophil with toxic granulation and Dohle body (arrow). (From Schumacher et al., 1984.)
Figure 7 Method for scanning a peripheral blood smear for a leukocyte differential count and RBC
and platelet morphology. (From Schumacher et al., 1984.)
F. Differential Count
The manual differential count is performed under oil immersion with a mechanical stage.
Usually 100 cells are counted, but some laboratories count 200 cells. The count is made in a
well-spread area of the slide (Fig. 3). The area should be about 1-2 em back from the tip of
the feathered portion of the slide. A common method for counting is to move across the slide,
perpendicular to the smear (Fig. 7).
Normal values for adults are shown in Table 1. At birth, the neutrophil-lymphocyte ratio
is similar to that of the adult. The ratio shows lymphocyte predominance from shortly thereafter
until 4 years of age, when the two cellular elements are equal. The ratio then rises to adult
levels by 6 years, where it remains.
The leukocytes observed in a normal differential are shown in Fig. 8. They are as follows.
1. The segmented neutrophil has a nucleus separated into definite lobes only by narrow
filaments. The cytoplasm is light pink and small, with evenly distributed light pink to
bluish-purple granules scattered throughout the cytoplasm.
2. The neutrophilic band often contains a C-shaped nucleus which is characteristically
nonfilamented, degenerative, and pyknotic at areas of future lobe formation. The cyto-
plasmic granules are similar to those of the neutrophil.
3. The eosinophil is about the size of a neutrophil and usually has a bandlike or two-lobed
nucleus. The cytoplasmic granules are spherical, uniform in size, and usually evenly
distributed throughout the cell. They stain bright reddish-orange with brownish tints.
Table 1 Normal Values for Differential White

Count in Adults
Absolute
Cell Percent (xl03 cum)
Neutrophils 40-80 1.5-8.0

Bands
Lymphocytes 15-45 1.0-4.8
Monocytes 0-12 0-1.0
Eosinophils 0-10 0-0.7
Basophils 0-4 1-0.2
'Included in the neutrophil percentage.

Figure 8 Cells observed in normal peripheral blood smear: A, erythrocytes; B, large lymphocyte with
azurophilic granules and deeply indented by adjacent erythrocytes; C, segmented neutrophil; D, eosinophil;
E, segmented neutrophil; F, monocyte with ground glass cytoplasm, coarse linear chromatin, and blunt
pseudopods; G, thrombocytes; H, lymphocyte; I, band neutrophil; J, basophil. (From Schumacher et a!.,
1984.)
4. The basophil has a round, indented band or tabulated nucleus. The cytoplasm contains dark
granules that are usually visible above, below, and lateral to the relatively light nucleus.
5. The monocyte is larger than the neutrophil and varies in shape from round to oval. The
nucleus is usually round, centriform, or kidney shaped, but may be deeply indented or
have two or more lobes separated by narrow filaments. The cytoplasm of monocytes
is dull gray-blue, and the cytoplasmic granules are usually fine, stained lightly bluish-
gray, numerous, and evenly distributed.
6. The lymphocytes in the peripheral blood vary in size from small (7-10 fJ.m) through
intermediate, to large, which are comparable in size to the granulocytes and mono-
cytes. The nucleus of the lymphocyte is usually round, but may be slightly indented.
The cytoplasm stains light to dark blue. Although most lymphocytes do not have true
granules, a few unevenly distributed, well-defined granules (lysosomes) may be noted.
These lysosomes are called azurophilic granules because they stained sky blue with
the original azure stains. However, with the current polychrome stains, the granules
are predominantly red.
Automated white cell differential counts are performed by pattern recognition or flow-
through cytochemical instruments. Pattern recognition uses image processing techniques and
evaluates numerous morphologic measurements. Some instruments employ high-resolution
color video scanning systems, which allow additional color analysis of the slide.
Early digital image processors analyzed blood smears placed on an automated microscope
stage. Automatic scanning began in a region of the smear where morphology was of good
quality. With some instruments, 100- 1000 cells could be counted. Automatic focusing made
the necessary adjustments while the instrument scanned the slide. Cells not recognized by the
instruments were flagged for review by the technologist. All data, including red cell morphol-
ogy, platelet estimate, and differential count, were presented on a summary data printout. The
printout was used by the technologist to review data prior to printing on the patient's ticket.
All data was checked prior to transmission to the central laboratory computer.
Today, a fully automated "walk away" image analyzer has reentered the automated PBS
arena. The MicroSystem 21 uses a neural network technology to scan a PBS and store all cells
seen (Fig. 9). Cells that do not meet criteria are reviewed on-screen by a technologist. Unlike
some predecessors, this new image analyzer now can also store several fields for RBC mor-
phology, which can facilitate the technologist's complete review of a PBS.
The pattern recognition process has the advantages of
1. Ability to screen large numbers of slides

2. Accuracy and precision for routine smears
3. Lack of error secondary to technologist fatigue
Its disadvantages are
1. Need for precise wedge or spun smears

2. Reduced efficiency when many abnormal smears are introduced into the system
Figure 9 MicroSystem 21, showing a WBC differential screen. Cells are classified by computer and
can be edited by a technologist. (From Intelligent Medical Imaging, with permission.)
Bayer : peroxidase and basophil channels Abbott: MAPPS, low and high angle;
polarized and depolarized light.

Coulter: VCS; impedance, conductivity, Sysmex: Direct current and radiofrequency
scatter
Roche: impedance and light absorption
Figure 10 Automated leukocyte classification cytogram schema.
3. High cost, requiring a high-volume laboratory to make such an instrument cost effec-
tive
4. May require use of proprietary stain
The flow-through cytochemical instruments produce leukocyte differentials based on cyto-

chemistry, light scatter, and conductivity (Fig. 10). Bayer Hl,H2 systems (formerly Technicon)
use myeloperoxidase (MPO) and basophil/lobularity (nuclear) analysis to enumerate and clas-
sify WBCs. Abbott Cell Dyn produces differentials by multiangle light scatter and a 90°-
depolarized scatter to separate eosinophils. This technology is known as multiangle polarized
scatter separation (MAPSS). Coulter uses volume, conductivity, and scatter (VCS) technology
to differentiate WBC populations. Sysmex systems differentiate WBCs by using direct current
(DC) and radiofrequency (RF). The Roche Cobas Argos 5 Diff uses impedance and light
absorption.
The flow-through cytochemical instrument has the advantages of
1. Increased precision, especially on leukopenic samples

2. Utilization of EDTA-anticoagulated blood
3. Ability to process large numbers of samples
4. Ability to count large numbers of cells in a short time period
5. Provides graphic representation of cell population
Its disadvantages are
1. Lack of recall of abnormal cells

2. Constant replacement of stain packs
3. Expense
These instruments are evolving into sophisticated analyzers combining the best flow cy-
tometry with expanded capabilities in precision and reproducibility, especially in the area of
blast identification.
All automated white cell differential counting instruments generate a large amount of data
which may be unnecessary. However, in large-volume laboratories, such instruments provide
the necessary screening for good patient care.
II. BONE MARROW

A. Introduction
Examination of the bone marrow by needle aspiration had been available since 1929, but it
was of limited value in assessing cellularity, topography, and focal disease. Bone marrow
biopsy was originally attempted by open surgery, in the form of a wedge biopsy. The technique
of needle biopsy of the bone marrow was first described in the late 1950s using Vim-Silverman
needles, commonly used for liver biopsies. Subsequent modifications by Jamshidi, Islam, and
others improved the quality of the sample obtained. Currently, the J-type needle, a modification
of Jamshidi's design, is most commonly used to obtain all the material needed for an accurate
evaluation of the bone marrow.
The manner in which bone marrow is obtained and processed is critical to the evaluation
of the specimen. A major emphasis in bone marrow pathology is the study of cytologic detail.
This can be accomplished only with optimal histopathologic processing of the specimen. Im-
proper handling may lead to serious difficulties in interpretation and, possibly, erroneous con-
clusions.
Erroneous conclusions may also be reached by "fuzzy logic." A bone marrow evaluation
and interpretation, even in the best of all possible worlds, is meaningless without clinical
correlation. All biopsy conclusions must always be drawn in association with a complete his-
tory and physical examination. Many findings have drastically different interpretations in dif-
ferent clinical settings. For example, blasts in the peripheral blood may be seen in a patient
with acute leukemia, but may also be identified in a patient on G-CSF therapy. An absolute
lymphocytosis, composed of small lymphocytes, is typical of chronic lymphocytic leukemia
(CLL), but is also characteristic of an acute pertussis infection.
B. Indications
Indications for bone marrow examination are many and varied, but in practically all situations
they are related to an abnormality in the peripheral blood that cannot be accounted for by any
preexisting medical condition. These abnormalities include anemia, thrombocytosis, leukocyto-
sis, cytopenia, peripheral dysplasia, and abnormal cells found within the peripheral blood.
The finding of a monoclonal spike on serum or urine protein electrophoresis, with or without
radiographic lytic lesions of bone, may indicate a bone marrow evaluation for workup of
multiple myeloma. Bone marrow aspiration and biopsy may also be useful in the investigation
of storage diseases, such as Gaucher's disease and Niemann-Pick disease, and in the identifica-
tion of malarial parasites, when the organisms are not identified in the peripheral blood.
Staging of patients with extramedullary disease processes is a further indication for bone
marrow examination. Neoplasias necessitating staging bone marrow biopsy include lympho-
mas, particularly Hodgkin's disease, and carcinomas. Special mention must be made at this
point of small cell carcinoma of the lung, as this particular tumor tends to disseminate early
in its course, with a high propensity for bone marrow. At the time of diagnosis, approximately
70% of patients with small cell carcinoma have evidence of metastatic disease. In these cases,
marrow evaluation in addition to bone scan has been found to be far superior to either tech-
nique alone, as bone scan evaluates cortical bone and bone marrow biopsy samples the medul-
lary cavity.
Certain disease processes, although traditionally subject to marrow examination, are no
longer considered indications for bone marrow biopsy. These include adult-onset idiopathic
thrombocytopenia purpura (ITP), iron deficiency anemia, B 12 and/or folate deficiency, polycy-
themia vera, and infectious mononucleosis. It is believed that these diagnoses can be made on
clinical grounds, with appropriate confirmatory laboratory studies.
Actual contraindications to bone marrow aspiration and biopsy are practically nonexistent.
The only causes of mortality reported from bone marrow needle aspiration and biopsy are due
to puncture of cardiac or vascular structures during a sternal approach. In neutropenic patients,
serious infection may occur at the biopsy site, although rarely. The formation of a localized
hematoma is also rare, even in thrombocytopenic patients, provided sustained pressure is ap-
plied after the procedure.
C. Procedure
As for any other consulting specialist, the first step in the performance of bone marrow aspira-
tion and biopsy is contact with the primary care physician. An open working relationship with
the clinician is vital, as a set of glass slides is not to be considered an inanimate "case," but a
patient waiting for potential treatment. Once a differential diagnosis has begun to take shape,
a full chart review is indispensable. Particular attention should be given to the patient's medical
history, any related conditions, medications, pertinent surgical and/or cytologic specimens, and
previous bone marrow biopsies with any available cytogenetic analyses. Finally, a recent com-
plete blood count (CBC) should be reviewed.
Preparation for any ancillary studies should be made in advance of the actual biopsy
procedure. Depending on the differential diagnosis, the patient may need any, or all, of the
ancillary studies outlined at the end of this chapter. The appropriate departments should be
contacted, in order to assure that they are aware a specimen is in transit, and also to find out
how much aspirated marrow is needed and how it is to be handled.
The most widely used instrument available for obtaining bone marrow biopsies, the J-type
needle, is patterned on the 1971 design by Jamshidi and Swaim (Fig. 11). These needles are
available in a variety of adult and pediatric sizes, and yield high-quality specimens with a wide
margin of safety. Used correctly, biopsy should involve only minor discomfort to the patient.
In general, bone marrow aspirate alone is taken from infants and children, as well as the
sternal site in adults. Bone marrow aspirate combined with biopsy is recommended for the
remainder of the population. The site chosen also depends on the age of the patient (Fig. 12).
In children less than 1 year of age, the anteromedial surface of the tibia is the preferred
location. On occasion, in older children and adults, the sternum, anterior iliac crest, or spinous
processes of the L1 or L2 vertebrae may be required. However, the great majority of marrow
aspirates and biopsies are obtained from the posterior superior iliac crest. This site provides a
large surface area for placement of the needle. The posterior superior iliac crest is remote from
vital organs, thereby minimizing the potential for complications.
Once the site has been selected, sterile technique must be observed. The skin over the
puncture site is shaved if necessary, and cleansed with a disinfectant solution. Then the skin,
subcutaneous tissue, and periosteum are infiltrated with a local anesthetic, such as 1% lido-
caine. The patient may experience a burning sensation or discomfort during infiltration. After
about 5 min, when the anesthetic has taken effect, the actual procedure may commence.
Although the general practice has been the reverse, current literature recommends that the
core biopsy always be obtained before marrow aspiration. Aspirating marrow with the biopsy
needle and then advancing the needle for biopsy may result in hemorrhage into the area of the
biopsy site, "aspiration artifact," leading to difficulties in interpretation and possibly erroneous
conclusions.
The bone marrow needle is inserted through the skin, subcutaneous tissue, and bony cor-
Figure 11 J-type bone marrow biopsy needle with stylet: left, biopsy needle with inserted obturator;
right, biopsy needle with obturator removed. Left to right: stylet, obturator, needle.
tex. Penetration of the cortex can be sensed by a sudden ease in advancing the needle. The
obturator of the needle is removed, and the needle is advanced. By gently replacing the obtura-
tor, an estimate of the biopsy size may be made. Review of published findings suggests that
the minimum adequate length of the biopsy material is in the range of 1.5- 2 em before tissue
processing. The needle is rocked to and fro, and then pulled back slightly, to be reinserted at
a slightly different angle, in order to detach the biopsy from the underlying bone. As the needle
is tapered at the distal end, the biopsy is removed by inserting the stylet into the distal end and
allowing the biopsy to exit from the hub.
Before placing the biopsy into fixative, up to 10 touch imprint preparations should be
made for routine Wright-Giemsa staining and possible other procedures, such as cytochemical
studies. Less damage to the biopsy specimen will result if the imprints are made by gently
touching a glass slide to the specimen rather than by squeezing the specimen with a forceps
and touching it to a slide. The touch preparations are allowed to air dry.
After obtaining the core biopsy, aspiration is performed by inserting the same or a smaller
needle through the same skin incision used for the biopsy, but placed on the periosteal surface
at a distance of approximately 1.0 em from the biopsy site. Once the needle is within the
marrow cavity, the obturator is removed and a 10-mL syringe is attached to the hub. Approxi-
mately 1.0 mL of fluid should be aspirated for morphologic studies. Increasingly larger quanti-
ties of aspirated material obtained contain logarithmically larger amounts of peripheral blood.
If more material is required, the needle should be repositioned. Smears should be made at the
bedside, using freshly obtained marrow (see "Preparation of Material"). These smears result in
better preservation of cellular detail than when the specimen is placed into anticoagulant. Addi-
tional material for ancillary studies should be placed into the appropriate transport medium.
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Chapter 1
THE MYSTERIOUS VISITOR
The forenoon of that momentous August day (how momentous time,
like unto some spirit-shaking vision, was soon and swiftly to show
us) had been bright and sunny. Snowy cumuli sailed along before a
breeze from the north. When the wind comes from that quarter here
in Seattle, it means good weather. But there was something sinister
about this one.
As the day advanced, the clouds increased in number and volume;
by noon the whole sky was overcast. And now? It was midafternoon
now; a gale from the south was savagely flinging and dashing the
rain against the windows, and it had become so dark that Milton
Rhodes had turned on one of the library-lamps. There was
something strange about that darkness which so suddenly had fallen
upon us.
"Too fierce to last long, Bill," observed Milton Rhodes, raising his
head and listening to the beating of the rain and the roar of the wind.
He arose from his chair, went over to one of the southern windows
and stood looking out into the storm.
"Coming down in sheets, Bill. It can't keep this up for very long."
I went over and stood beside him.
"No," I returned; "it can't keep this up. But, rain or sun, our trip is
spoiled now."
"For today, yes. But there is tomorrow, Bill."
But, in the sense that Milton Rhodes meant, there was to be no
tomorrow: at the very moment, in the midst of the roar and the rage
of the elements, Destiny spoke, in the ring of a telephone-bell—
Destiny, she who is wont to make such strange sport with the lives of
men. I sometimes wonder if stranger sport any man has ever known
than she was to make with ours.
"Wonder who the deuce 'tis now," muttered Milton Rhodes as he left
the room to answer the call.
I remained there at the window. Of that fateful conversation over the
wire, I heard not so much as a single syllable. I must have fallen into
a deep reverie or something; at any rate, the next thing I knew there
was a sudden voice, and Milton Rhodes was standing beside me
again, a quizzical expression on his dark features.
"What is it, Bill?" he smiled. "In love at last, old tillicum? Didn't hear
me until I spoke the third time."
"Gosh," I said, "this is getting dreadful! But—"
"Well?"
"What is it?"
"Oh, a visitor."
I regarded him for a moment in silence.
"You don't seem very enthusiastic," I observed.
"Why should I be? Some crank, most likely. Must be, or he wouldn't
set out in such a storm as this is."
"Great Pluvius, is he coming through this deluge?"
"He is. Unless I'm mighty badly mistaken, he is on his way over right
now."
"Must be something mighty important."
"Oh, it's important all right, important to him," said Milton Rhodes.
"But will it interest me?"
"I'll tell you that before the day is done. But who is this queer
gentleman?"
"Name's Scranton, Mr. James W. Scranton. That's all that I know
about him, save that he is bringing us a mystery. He called it a
terrible, horrible scientific mystery."
"That," I exclaimed, "sounds interesting!"
It was patent, however, that Milton Rhodes was not looking forward
to the meeting with any particular enthusiasm.
"It may sound interesting," he said; "but will it prove so? That is the
question, Bill. To some people, you know, some very funny things
constitute a mystery. Mr. James W. Scranton's mystery may prove to
belong to that species. We must wait and see. Said that he had
heard of me, that, as I have a gift (that is what he called it, Bill, a gift)
of solving puzzles and mysteries, whether scientific, psychic, spooky
or otherwise—well, he had a story to tell me that would eclipse any I
ever had heard, a mystery that would drive Sherlock Holmes himself
to suicide. Yes, that's what he really said, Bill—the great Sherlock
himself to suicide."
"That's coming big!" I said.
Milton Rhodes smiled wanly.
"We haven't heard his yarn yet. We can't come to a judgment on
such uncertain data."
"Scranton," said I. "Scranton. Hold on a minute."
"What is it now?"
"Wonder if he belongs to the old Scranton family."
"Never heard of it, Bill."
"Pioneers," I said. "Came out here before ever Seattle was founded.
Homesteaded down at Puyallup or somewhere, about the same time
as Ezra Meeker. It seems to me—"
"Well?" queried Milton Rhodes after some moments, during which I
tried my level best to recollect the particulars of a certain wild,
gloomy story of mystery and death and horror that I had heard long
years before—in my boyhood days, in fact.
"I can not recollect it," I told him. "I didn't understand it even when I
heard the man, an old acquaintance of the Scrantons, tell the story—
a story of some black fate, some curse that had fallen upon the
family."
"So that's the kind of mystery it is! From what the man said, though
that was vague, shadowy, I thought that it was something very
different. I thought that it was scientific."
"Maybe it is. We are speculating, you know, if one may call it that, on
pretty flimsy data. One thing: I distinctly remember that Rainier had
something to do with it."
"What Rainier?"
"Why, Mount Rainier."
"This is becoming intriguing," said Milton Rhodes, "if it isn't anything
else. You spoke of a black fate, a curse: what has noble Old He, as
the old mountain-men called Rainier, to do with such insignificant
matters as the destinies of us insects called humans?"
"According to the old fellow I mentioned, that old acquaintance of the
Scrantons, it was there, on Rainier, that this dark and mysterious
business started."
"What was it that started?"
"That's just it. The man didn't know himself what had happened up
there."
"Hum," said Milton Rhodes.
"That," I went on, "was many years ago. It was just, I believe, after
Kautz climbed the mountain. Yes, I am sure he said 'twas just after
that. And this man who told us the story—his name was Simpson—
said 'twas something that Scranton learned on Kautz's return to
Steilacoom that led to his, Scranton's, visit, to Old He. Not from
Kautz himself, though Scranton knew the lieutenant well, but from
the soldier Hamilton."
"What was it that he learned?"
"There it is again!" I told him. "Simpson said he could tell what that
something was, but he told us that he would not do so."
"A very mysterious business," smiled Milton Rhodes. "I hope that our
visitor's story, whatever it is, will prove more definite."
"Wasn't it," I asked, "in the fifties that Kautz made the ascent?"
"In July, 1857. And pretty shabbily has history treated him, too. It's
always Stevens and Van Trump, Van Trump and Stevens. Why, their
Indian, Sluiskin, is better known than Kautz!"
"But I thought," said I, "that Stevens and Van Trump were the very
first men to reach the summit of Mount Rainier."
"Oh, don't misunderstand me, Bill," answered Milton Rhodes. "All
honor to Stevens and Van Trump, the first of men to reach the very
top of the mountain; but all honor, too, to the first white man to set
foot on Rainier, the discoverer of the great Nisqually Glacier, the first
to stand upon the top of Old He, though adverse circumstances
prevented his reaching the highest point."
"Amen," said I—as little dreaming as Kautz, Stevens and Van Trump
themselves had ever done of that discovery which was to follow, and
soon now at that.
For a time we held desultory talk, then fell silent and waited.
There was a lull in the storm; the darkness lifted, then suddenly it fell
again, and the rain began to descend with greater violence than
ever.
Milton Rhodes had left his chair and was standing by one of the
eastern windows.
"This must be our visitor, Bill," he said suddenly.
I arose and went over to his side, to see a big sedan swinging in to
the curb.
"Yes!" exclaimed Rhodes, his face beginning to brighten. "There is
Mr. James W. Scranton.
"Let us hope, Bill," he added, "that the mystery which he is bringing
us will prove a real one, real and scientific."
The next moment a slight figure, collar up to ears, stepped from the
car and headed swiftly up the walk, leaning sidewise against the
wind and rain.
"'Now is the dramatic moment of fate, Watson'," quoted Milton
Rhodes with a smile as he started towards the door, "'when you hear
a step upon the stair which is walking into your life, and you know
not whether for good or ill'."
Chapter 2
WHAT HE TOLD US
A few moments, and Milton Rhodes and his visitor entered the room.
"My friend Mr. Carter," Rhodes remarked to Mr. James W. Scranton
as he introduced us, "has assisted me in some of my problems; he is
my colleague, so to say, and you may speak with the utmost
confidence that your story, if you wish it so, will be held an utter
secret."
"For the present, I wish it to be a secret," returned Scranton, seating
himself in the chair which Rhodes had pushed forward, "and so
always if no discovery follows. If, however, you discover things—and
I have no doubt that you will do so—why, then, of course, you may
make everything public where, when and in whatsoever manner you
wish."
"And so," said Milton, "you bring us a mystery—a scientific mystery."
"Yes, Mr. Rhodes. It is scientific, and I believe that it will prove to be
something more. In all probability stranger than any which any man
on this earth has ever known."
There was not the slightest change on Milton Rhodes' features, and
yet I could have sworn that a slight fleeting smile had touched them.
I turned my look back to our visitor, and I saw upon his face an
expression so strange that I stared at him in something very like
surprise.
What was it that this man was going to tell us?
Soon that expression was gone, though its shadow still rested on his
thin and pale features.
"This mystery of which I have come to tell you," he said suddenly, "is
an old, old one."
I glanced at Milton Rhodes.
"Then why," he asked, "bring it to me?"
An enigmatic smile flitted across Scranton's face.
"Because it is new as well. You will soon see what I mean, Mr.
Rhodes. You will see why, after all these years, I suddenly found
myself so anxious to see you that I couldn't even wait until this storm
and deluge ended."
From the inside pocket of his coat he drew a leather-covered
notebook, much worn and evidently very old.
"This," said he, holding the book up between thumb and forefinger,
"is the journal kept by my grandfather, Charles Scranton, during his
journey to, and partial ascent of, Mount Rainier in the year 1858."
Milton Rhodes glanced over at me and said:
"Our little deduction, Bill, wasn't so bad, after all."
Scranton turned his eyes from one to the other of us with a
questioning look.
"Mr. Carter," Rhodes explained, "was just telling me about that trip,
and he wondered if you belonged to the old pioneer Scranton family."
"This," exclaimed the other, "is something of a surprise to me! Few
people, I thought, very few people, even knew of the journey."
"Well, Mr. Carter happens to be one of the few."
"May I ask," said Scranton, addressing himself to me, "how you
learned that my grandfather had visited the mountain? And what you
know?"
"When I was a boy, I heard a man—his name was Simpson—tell
about it."
"Oh," said Scranton, and it was as though some fear or some thing
of dread had suddenly left him.
"His story, however," I added, "was vague, mysterious. Even at the
time I couldn't understand what it was all about."
"Of course. For, though Simpson knew of the journey, he knew but
little of what had happened. And more than once did I hear my
grandfather express regret that he had told Simpson even as much
as he had. I suppose there was something, perhaps a great deal, of
that I-could-tell-a-lot-if-I-wanted-to in Simpson's yarn."
"There was," I nodded.
"The man, however, knew virtually nothing—in fact, nothing at all
about it. I have no doubt, though, that he did a lot of guessing. I don't
believe that my grandfather, dead these many years now, ever told a
single living soul all. And, as for all that he told me—well, I can't tell
everything even to you, Mr. Rhodes."
A strange look came into the eyes of Milton Rhodes, but he
remained silent.
Scranton raised the notebook again.
"Nor is everything here. Nor do I propose to read everything that is
here. Just now the details do not matter. It is the facts, the principal
facts, with which we have to do now. This record, if you are
interested—and I have no doubt that you will be—I shall leave in
your hands until such time as you care to return it to me.
"Now for my grandfather's journey.
"With three companions, he left the old homestead near what is now
Puyallup, on the 16th of August, 1858. At Steilacoom, they got an
Indian guide, Sklokoyum by name. The journey was made on
horseback to the Sick Moon Prairie.[3] There the animals were left,
with one man to guard them, and my grandfather, his two
companions and the Indian—this guide, however, had never been
higher up the Nisqually River than Copper Creek—set out on foot for
the mountain."
"One moment," Milton Rhodes interrupted. "According to that
Simpson, it was something that your grandfather heard from the
soldier Hamilton, and not from Kautz himself, that led to his making
this journey to Mount Rainier. Is that correct?"
"Yes; it is correct."
"May I ask, Mr. Scranton, what it was that he learned?"
Again that enigmatic smile on Scranton's face. He tapped the old
journal.
"You will learn that, Mr. Rhodes, when you read this record."
"I see. Pray proceed."
Chapter 3
THE MYSTERY OF OLD HE
"It was about three o'clock in the afternoon of the 24th," said
Scranton, "that they reached the foot of the Nisqually Glacier, called
Kautz Glacier by my grandfather. As for what followed, I shall give
you that in my grandfather's own words."
He opened the book, at a place marked with a strip of paper, and
read from it the following:
"August 24th, 10 p.m.—At last we are on the mountain. And how can
I set it down—this thing that has happened? What I write here must
be inadequate indeed, but I shall not worry about that, for a hundred
years could never dim the memory of what I saw. I have often
wondered why the Indians were afraid of Rainier; I know now. And
what do I really know? I know what I saw, I know what happened; but
only God in Heaven knows what it means.
"Got started early. Still following the river. Going very difficult.
Crossed stream a number of times and once had to take to the
woods. Reached the glacier about three o'clock—an enormous wall
of dirty ice, four or five hundred feet in height, with the Nisqually
flowing right out of it. Day had turned dark and threatening. Climbed
the eastern wall of the cañon. Clouds suddenly settled down—a fog
cold and thick and dripping—and we made camp by a tiny stream,
near the edge of the cañon cut by the glacier. Soon had a good fire
burning. And it was not long before it came—the shrouded figure and
with it that horrible shape, 'if,' as old Milton has it in Paradise Lost,
'shape it might be called that shape had none.'
"At times the fog would settle down so thick we could see no farther
than fifty feet. Then suddenly objects could be made out two or three
hundred feet away. At the moment the fog was about us thicker than
ever. We were sitting by the fire, warming ourselves and talking—
White, Long and myself. All at once there was an exclamation. I
looked at Long, and what I saw on his face and in his eyes brought
me to my feet in an instant and whirled my look up in that direction in
which he was staring.
"And there on the top of the bank, not more than thirty feet from us,
stood a tall, white, shrouded figure, a female figure, and beside it,
seemingly squatting like a monstrous toad, was that dark shape that
had no shape. But, though shape it had none, it had eyes—big eyes
that burned at us with a greenish, hellish fire.
"White snatched up his rifle and thrust it forward, but I stepped over
and shoved the muzzle aside. When we looked up there again, the
woman, for a woman, a white woman too, it certainly was—well, she
was gone, and with her that formless thing with the hellish fire in its
big eyes.
"'What was it?' exclaimed White.
"He rubbed his eyes and stared up there again, then this way and
that, all about into the thick vapor.
"'Was it only a dream?'
"'It was real enough,' I told him. 'It was a woman, a white woman.'
"'Or,' put in Long, 'the spirit of one.'
"'I know one thing,' said White: 'she may be a flesh-and-blood
creature, and she may be a spirit; but that thing that crouched there
beside her was not of this world of ours!'
"He shuddered.
"'Not of this world of ours! Men, what was that thing?'
"That, of course, was a question that neither Long nor myself could
answer.
"'If,' I said, 'it hadn't been for this fog! If we could only have seen
them better!'
"Of a sudden White exclaimed:
"'Where's Sklokoyum?'
"'Not far,' I told him. 'Say—he was up there, up there where they
came from. Come, let's look into this.'
"I sprang up the bank. They followed. A moment, and we were in
that very spot where the woman and the thing had stood so brief a
space before.
"'It was no dream, at any rate,' observed Long, pointing to the
crushed purple flowers—a species, I believe, of aster.
"'No,' I returned; 'it was not a dream.'
"'Maybe,' said White, peering about, 'we'll wish, before this business
is ended, that it all had been a dream.'
"Came a loud scream from above. Silence. And then the crash of
some heavy body through the branches and shrubs.
"'Sklokoyum!' I cried.
"White's hand closed on my arm with the grip of a vice.
"'Hear that?'
"I heard it. It was the voice of a woman or a girl.
"'She's calling,' said Long, 'calling to it.'
"'Great Heaven!' I exclaimed. 'It's after the Indian! Come!'
"I started up, but I had taken only a half-dozen springs or so when
Sklokoyum came leaping, plunging into view. I have seen fear,
horrible fear, that of cowards and the fear of brave men; but never
had I, never have I, seen anything like that fear which I saw now.
And Sklokoyum, whatever his faults, has a skookum tumtum—in
other words, is no coward.
"Down the Indian came plunging. There was a glimpse of a blood-
covered visage; then he was past. The next instant a shock, a
savage oath from White, and he and the Siwash fell in a heap, went
over the edge and rolled down the bank and clean to the fire.
"Long and I followed, keeping a sharp lookout behind us, and,
indeed, in every direction. But no glimpse was caught of any moving
thing, nor did the faintest sound come to us from out that cursed
vapor, settling on the trees and dripping, dripping, dripping.
"Sklokoyum's right cheek was slashed as though by some great
talon, and he had been terribly bitten in the throat.
"'A little more,' observed Long, 'and it would have been the jugular,
and that would have meant klahowya, Sklokoyum.'
"The Indian declared that he had been attacked by a demon, a klale
tamahnowis, a winged fiend from the white man's hell itself. What
was it like? Sklokoyum could not tell us that. All he knew was that
the demon had wings, teeth a foot in length and that fire shot out of
its eyes and smoke belched from its nostrils. And surely it would
have killed him (and I have no doubt that it would have) if an angel,
an angel from the white man's Heaven, had not come and driven it
off. What was the angel like? Sklokoyum could not describe her, so
wonderful was the vision. And her voice—why, at the very sound of
her voice, that horrible tamahnowis flapped its wings and slunk away
into the fog and the gloom of the trees.
"Poor Sklokoyum! No wonder he gave us so wild an account of what
had happened up there! And, said he, to remain here would be
certain death. We must go back, start at once. Well, we are still here,
and we are not going to turn back at this spot, though I have no
doubt that Sklokoyum himself will do so the very first thing in the
morning.
"The fog is thinning. Now and again I see a star gleaming down with
ghostly fire. We came here seeking a mystery; well, we certainly
have found one. I wonder if I can get any sleep tonight. Long is to
relieve me at twelve o'clock. For, of course, we can not, after what
has happened, leave our camp without a guard. And I wonder if—
what, though, is the good of wondering? But what is she,
Sklokoyum's angel? And what is that klale tamahnowis, that demon?
And where is the angel now?"
Chapter 4
"VOICES!"
Scranton closed the journal on the forefinger of his right hand and
looked at Milton Rhodes.
"Well," said he, "what do you think of that?"
Rhodes did not say what he thought of it. I thought that I knew,
though I had to acknowledge that I wasn't sure just what I thought of
this wild yarn myself.
After a little silence, Milton Rhodes asked:
"Is that all?"
"All? Indeed, no!" returned Scranton.
He opened the book and prepared to read from it again.
"This adventure that I have just read to you," he said looking over the
top of the journal at Milton Rhodes, "took place in what is now known
as Paradise Park—a Paradise where, as you well know, there is
sometimes twenty-five feet of snow in the winter."
"Of course that was the place," Milton nodded, "for they had climbed
the eastern wall of the cañon and had camped near the edge."
"And the one that followed," Scranton added, "on what we now call
the Cowlitz Glacier. I believe, Mr. Rhodes, that you have visited
Rainier a number of times?"
"Many times, Mr. Scranton. Few men, I believe, know the great
mountain better than I do; and I never followed in the footsteps of a
guide, imported or otherwise, either."
"Then, in all likelihood, you know the Tamahnowis Rocks in the
Cowlitz Glacier."
"I have been there a dozen times."
"Did you ever, Mr. Rhodes, notice anything unusual at that place?"
"Nothing whatever. I found the ascent of the rocks themselves rather
difficult and the crevasses there interesting, but nothing more."
"Well, it was there," said Scranton, "that what I am going to read to
you now took place. Yes, I know that it was there at the Tamahnowis
Rocks, though I myself never could find anything there, either. And
now, after all these long years, once more it is in that very spot that
—"
He broke off abruptly and dropped his look to the old record.
Milton Rhodes leaned forward.
"Mr. Scranton," he asked, "what were you going to say?"
Scranton tapped the old journal with a forefinger.
"This first," he said. "Then that."
"The story begins to take shape," observed Milton Rhodes; and I
wondered what on earth he meant. "Pray proceed."
Whereupon the other raised the book, cleared his throat with an
ahem and started to read to us this astonishing record:
"August 25th.—I was right: the very first thing in the morning the
Indian left us. Nothing could induce him to go forward, to remain at
the camp even. The demons of Rainier would get us, said he, if we
went on—the terrible tamahnowis that dwelt in the fiery lake on the
summit and in the caverns in the mountain side, caverns dark and
fiery and horrible as the caves in hell itself. Had we not had warning?
One had come down here, even among the trees, and undoubtedly it
would have killed us all had it not been for that angel. He,
Sklokoyum, would not go forward a single foot. He was going to
klatawah hyak kopa Steilacoom. How the old fellow begged us to
turn back, too! It was quite touching, as was his leave-taking when
he finally saw that we were determined to go on. Old Sklokoyum
acted as though he was taking leave of the dead—as, indeed, he
was. And at last he turned and left us, and in a few minutes he had
vanished from sight.
"How I wish to God now that we had gone back with him!"
At this point, Scranton paused and said:
"The Indian was never seen again or even heard of again."
The account (which I am copying from the journal itself) went on
thus:
"Fog disappeared during the night. A fairer morning, I believe, never
dawned on Rainier. Sky the softest, the loveliest of blues. A few
fleecy clouds about the summit of the mountain, but not a single wisp
of vapor to be seen anywhere else in all the sky.
"Proceeded to get a good survey of things. From the edge of the
cañon, got a fine view clear down the glacier and clear up it, too. Ice
here covered with dirt and rock-fragments, save a strip in the middle,
showing white and bluish. Badly crevassed. It must have been right
about here that Kautz left the glacier. He climbed the cliffs on the
other side, and then, the next morning, he started for the top. It
seemed, to us, however, that the ascent could be made more easily
on this side. But we were not headed for the summit; we had a
mystery to solve, and we immediately set about trying to do it.
"We started to trail them—the angel and that thing with the big eyes
that burned with a greenish, hellish fire. Where they had crushed
through the flower-meadows, this was not difficult. At other places,
however, no more sign than if they had moved on through the air
itself. One thing was soon clear: they had held steadily upward,
never swinging far from the edge of that profound cañon in which
flows that mighty river of ice.
"The ground became rocky. No sign. Then at last, in a sandy spot,
we suddenly came to the plain prints left by the feet of the angel as
she passed there, and, mingled with those prints, there were marks
over which we bent in perplexity and then in utter amazement.
"These marks were about eight inches in length, and, as I looked at
them, I felt a shiver run through me and I thought of a monstrous bird
and even of a reptilian horror. But that squatting form we had seen
for those few fleeting moments—well, that had not been either a bird
or a reptile.
"'One thing,' said Long, 'is plain: it was leading and the angel was
following.'
"White and I looked closely, and we saw that this had certainly been
so.
"'It appears,' Long remarked, 'that the fog didn't interfere any with
their journey. They seem to have gone along as steadily and surely
as if they had been in bright sunshine.'
"'I wonder,' White said, 'if the thing was smelling the way back like a
dog.'
"'Back where?' I asked. 'And I see no sign of a down trail.'
"'Lord,' exclaimed Long, looking about uneasily, 'the Siwashes say
that queer things go on up here, that the mountain is haunted; and,
blame me, if I ain't beginning to think that they are right! Maybe,
before we are done, we'll wish that we had turned back with old
Sklokoyum.'
"I didn't like to hear him talk like that. He spoke as though he were
jesting, but I knew that superstitious dread had laid a hand upon him.
"'Nonsense!' I laughed. 'Haunted? That woman that we saw and that
thing—well, we know that they were real enough, and we knew that
even when we didn't have these footprints to tell us.'
"'Oh, they are real, all right,' said Long. 'But real what?'
"A little while after that, we came to a snowfield, an acre or two in
extent, and there we made a strange discovery. The trail led right
across it. And it was plain that it had still been leading and the angel
had been following. Of a sudden White, who was in advance,
exclaimed and pointed.
"'Look at that,' he said. 'See that? Its tracks end here.'
"And that is just what they did! But the tracks of the angel went right
on across the snow.
"'Where did the thing go to?' I wondered.
"'Perhaps,' suggested Long, 'she picked it up and carried it.'
"But I shook my head.
"'A woman—or a man either, for the matter of that—carrying that
thing!' White exclaimed. 'She could never have done that. And you
can see for yourself; she never even paused here. Had she stopped
to pick the thing up—what a queer thought—we would have the story
written here in the snow.'
"'Then,' said Long, 'it must have gone on through the air.'
"'Humph!' White ejaculated. 'Through the air! Well, Sklokoyum said
that the thing has wings—the bat wings of the white man's devil!'
"'But,' I objected, 'Sklokoyum was so badly scared that he didn't
know what he saw.'
"'I wonder,' said White.
"Beyond the snowfield, the place was strewn in all directions with
rock-fragments. It was comparatively level, however, and the going
was not difficult. A tiny stream off to the right, a steep rocky mass
before us. We were soon, having crossed the stream, ascending
this. It was a steep climb, but we were not long in getting up it. At this
place we passed the last shrub. We figured that we must be near an
altitude of seven thousand feet now. Dark clouds forming. At times,
in a cloud-shadow, the place would have a gloomy and wild aspect.
No trail, though at intervals we would find a disturbed stone or faint
marks in the earth. Our route lay along a broken ridge of rock. On
our left the land fell away toward Kautz's Glacier [the Nisqually] while
on the right, coming up close, was another glacier [the Paradise]
white and beautiful.
"Ere long we reached a point where the ridge had a width of but a
few yards, a small glacier on the left, the great beautiful one on the
other side. And here we found it, found the trail of the thing and
Sklokoyum's angel. They had come up along the edge of the ice on
our left (to avoid the climb up over the rocks) crossed over the ridge
(very low at this point) and held steadily along the glacier, keeping
close to the edge. And in that dense fog! And just to the right the ice
went sweeping down, like a smooth frozen waterfall. A single false
step there, and one would go sliding down, down into yawning
crevasses. How had they done it? And to where had they been
going, in this region of barren rock and eternal snow and ice, through
that awful fog and with night drawing on?
"There was but one way to get the answer to that, and that was to
follow.
"And so we followed.
"And how can I set down here what happened? I can not. I simply
can not. Not that it matters, for it can never, in even the slightest
feature, fade from my mind. It may be that I shall find myself wishing
that some of it would.
"Clouds grew larger, thicker, blacker. The change was a sudden,
sinister one; there seemed to be something uncanny about it even.
Our surroundings became gloomy, indescribably dreary and savage.
We halted, there in the tracks of the thing and the angel, and looked
about us, and we looked with a growing uneasiness and with an awe
that sent a chill to the heart—at any rate, I know that it did to mine.
"White and Long wanted to turn back. Clouds had fallen upon the
summit of Rainier and were settling lower and lower. Viewed from a
distance, they are clouds, but, when you find yourself in them, they
are fog; and to find our way back in fog would be no easy matter.
However, so I objected, it would be by no means impossible. There
would be no danger, I said, if we were careful.
"'There is that pile of rocks,' I added, pointing ahead. 'Let's go on to
that at any rate. The trail seems to lead straight towards those rocks.
I hate to even think of turning back now, now when we are so near.'
"Still, I noted with some uneasiness, my companions hesitated, their
minds, I suppose, a prey to feelings for which they could not have
found a rational explanation. All this, however, really was not
strange, for it was truly a wild and savage and awesome place and
hour.
"At length, in an evil moment, we moved forward.

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