Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy

Dennis O’Malley, MD 1/12

SIMULATORS OF MALIGNANCY IN BONE MARROW

Simulators of malignancy are an important area in bone marrow pathology. The prime
issue is overdiagnosing a benign condition, which could lead to over treatment of a
potentially benign condition. Recognition of such conditions can be very important in
patient management.

Below, I will discuss several important benign mimics of malignant disorders. Distinction
of these processes from their malignant mimics will be emphasized.

Megaloblastic Anemia:

Historically, megaloblastic anemia has been referred to as ‘pseudoleukemia’, and not

without good reason. Although mild cases of megaloblastic anemia are relatively easy to
evaluate, cases with severe changes can appear quite disturbing, even to the most
experienced pathologist. As in all cases, it is quite important to correlate clinical and
laboratory findings to arrive at this diagnosis. The peripheral blood will almost always
have a markedly elevated MCV (often >120 fL), although concurrent iron deficiency may
cause a lower MCV than expected. There may be nucleated red blood cells, large, bizarre,
left-shifted myeloid cells, and large and giant platelets. All cell lineages may have
‘dysplasia’, meaning that they may have nuclear and/or maturation abnormalities that
correspond to those seen in neoplastic conditions. The core biopsy can be quite striking
and probably the most disturbing of all the findings. Due to a relative erythroid
hyperplasia and a lack of maturation, there are sheets and clusters of large immature cells
in the marrow. The distinction of these immature erythroids from myeloblasts can be
difficult. Subtle diagnostic clues are that erythroid precursors are almost always perfectly
round; they have very delicate chromatin, often with accentuation at the rim. Review of
the aspirate smears usually can reliably distinguish from the very worrisome appearance
of the core biopsy. In the aspirate, the erythroid nature of the immature cells becomes
more apparent. However, in the most severe cases, the cells in the aspirate may look like
poorly differentiated blasts, of unknown type. In these cases ancillary studies are of great
value. Foremost, performing either hemoglobin or glycophorin immunohistochemical
stains may positively identify the cells as erythroid. Lack of flow cytometric or
immunohistochemical evidence of a blast phenotype can be reassuring. The
differentiation from erythroleukemia (‘pure erythroid leukemia’) would be a rare
difficulty. In these cases, strict application of the WHO diagnostic criteria would be
helpful. Cytogenetic abnormalities are almost always seen in erythroleukemia; aberrant
PAS staining in erythroblasts, and severe dysplastic features would favor a leukemic
diagnosis. Integration with clinical findings and the course of the disease would also be
useful.

Cytokine Effects:

Cytokines seem to have become as ubiquitous as aspirin. Most commonly, we see

treatment of patients with granulocyte-colony stimulating factor (G-CSF),
granulocyte/monocyte-colony stimulating factor (GM-CSF), and erythropoietin. Less
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 2/12

often, marrow treated with a variety of interleukins can show striking changes as well.
With all of these treatments, the increase in immature cells and cellularity can mimic
neoplastic marrow conditions. Most often, they simulate AML (Table 1), but occasionally
MDS or MPDs can be considered as well. The single most important factor in these
conditions is obtaining an appropriate clinical and treatment history. This can resolve
most difficulties.

GM-CSF and G-CSF will cause increases in immature cells in the peripheral blood.
These typically include left-shifted myeloid elements in a variety of stages of maturation.
Quite often, these cells will have excessive toxic granulation. In the marrow, there will
usually be an increase in the M:E ration, with an excess of immature myeloid elements.
There may be other, non-specific ‘dysplastic’ changes seen in granulocytes as well. With
GM-CSF, there are often increased monocytes and monocytic precursors. In both, there is
preponderance of maturing myeloid forms, but with only a modest increase in blasts. The
predominant cells are mostly promyelocytes and myelocytes. They will often have toxic
granulation. There is usually not a maturation arrest, but simply a relative increase in the
number of immature forms.

Very rarely, an acute leukemia will be response to cytokine effect. I have seen cases
where patients with low WBC will be treated with G-CSF by well-intentioned physicians,
only to present with blast counts in the hundreds of thousands.

The effects of erythropoietin (Epo) only rarely cause diagnostic difficulty. There is a
predictable increase in erythroid precursors. This will cause a decrease in the M:E ratio
and a relative increase in the erythroid cell seen in the marrow. The increased immature
erythroids may appear concerning on core biopsies, but are usually easily identifiable in
aspirate smears. If difficulty remains, immuno stains for erythroid derivation may be of
benefit. At high levels, Epo drives megakaryopoiesis, so megakaryocytes may appear
increased as well.

Toxins:

The effect of toxins on marrow depends on the agent. Benzene, a well known
troublemaker, may cause aplastic anemia. Pesticide exposure may also cause transient
marrow aplasia. The aplastic marrows are not in themselves difficult to diagnose. Rather,
the recovery from a toxic insult can be very troublesome. In these cases, the marrow
tends to recover in ‘waves’. The most concerning finding is a marrow with a reactive
hyperplasia of synchronized myeloid precursors. Finding a massive marrow population,
all at the same stage of maturation can be quite concerning, and raise a differential of
AML or APML. In these cases, clinical correlation may be the key. In the few cases I
have seen, the myeloid cells appeared to be morphologically normal promyelocytes.
These cells did not appear to have the morphologic abnormalities associated with APML
(folded nuclei, Auer rods). Further investigation of clinical history for toxin or drug
exposures may resolve difficult cases that simply don’t seem to be leukemia.
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 3/12

Ethanol has a whole host of deleterious bone marrow effects. Besides it role in
megaloblastic anemias, ethanol has a direct suppressive effect on bone marrows. It is
often associated with some degree of marrow hypoplasia. In addition it has associated
plasmacytosis, typically mild (<10%). Chronic ethanol use may induce the formation of
ringed sideroblasts, and probably is a more common cause of this finding than MDS. It
may also rarely cause sideroblastic anemia, with ringed sideroblasts, megaloblastic
changes and anemia – directly mimicking refractory anemia with ringed sideroblasts. The
rare finding of plasma cell iron may be a diagnostic clue. Clinical history and a check of
liver enzyme tests may be of benefit as well.

Chemotherapy can cause a variety of marrow changes that appear quite dysplastic. All of
the changes seen in myelodysplasia in the erythroid series can be replicated by
chemotherapy. It is important to keep in mind that chemotherapy typically consists of
antimetabolite drugs. Marrow, being metabolically active, can be easily affected by these
medications. In any drug where anemia or myelosuppression can occur (essentially all
chemotherapy agents), ‘dysplasia’ can be seen in the marrow.

HIV/AIDS:

The marrow changes in HIV/AIDS marrows are protean. Because of drug effects,
infectious diseases, reactive changes and the viral changes themselves, HIV/AIDS
marrows can mimic almost any neoplasm.

Lymphocytosis, with atypical lymphocytes, poorly formed germinal centers, and extreme
plasmacytosis can all be seen in HIV/AIDS marrows. In these cases, applications of
immunohistochemical stains, and flow cytometry are most useful.

Mimicry of MDS is not uncommon in HIV/AIDS. Studies have shown that the
‘dysplasia’ seen in MDS is only very rarely premalignant, and is usually due to other
causes including HIV infection. The marrows are often hypercellular with peripheral
cytopenias. The changes include a left shift of myeloid components but only a marginal
increase in blasts. The erythroid series may show megaloblastoid changes,
multinucleation, fragmentation and budding but these effects are usually secondary to
therapies. Megakaryocytes are directly infected by HIV and act as a reservoir for the
virus. They can be unilobate, have coarse, abnormal chromatin and bizarre shapes. The
so-called ‘naked megakaryocyte nucleus’ is quite distinctive and when numerous, can
suggest a diagnosis of HIV/AIDS. Marrow fibrosis, usually mild or moderate, is seen in
most marrows in HIV/AIDS.

Infectious agents of a variety of types can be seen in HIV/AIDS marrows. They may
present confusing or unusual marrow findings that can mimic lymphomas, sarcomas or
epithelial malignancies. Clinical suspicion, culture results and the use of organism stains
can be quite beneficial. I personally perform infectious disease stains (PAS, GMS, AFB)
on all HIV/AIDS marrows because of increased likelihood of infectious disorders. I also
perform an immunohistochemical stain for Parvovirus B19, which can be a cause of
chronic anemia in HIV/AIDS patients.
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 4/12

Benign plasmacytosis:

Plasmacytosis is a relatively common finding in bone marrows. It rarely reaches levels

that are of clinical concern (above about 5%). However, even mild plasmacytosis will
occasionally overlap the entity monoclonal gammopathy of undetermined significance
(MGUS). The most valuable distinction between a mild, benign plasmacytosis and
MGUS is either: 1) the presence of monoclonality by kappa/lambda light chain staining
or 2) the presence of a monoclonal serum immunoglobulin protein. In almost all
situations, these plasma cells will be morphologically benign (e.g. small and mature-
appearing). When ‘malignant’ features are seen, more clinical concern may be raised.
Features of abnormal plasma cells include: more than occasional binucleation,
multinucleation (more than two nuclei), centrally-placed nuclei, nucleoli, blastic
chromatin, or anaplasia. Immunoglobulin inclusions can be seen in both benign and
malignant plasma cells. Excess numbers of flame cells, Mott cells or Russell bodies, or
more than very rare Dutcher bodies may signal malignancy.

There are rare benign conditions that cause an excess of plasma cells. These are typically
mature in appearance, but may reach numbers that would cause plasma cell myeloma to
be considered (Table 2). In cases of hepatitis, especially hepatitis C, plasma cells can
number up to 30-40% in the marrow cells. Chronic infections, autoimmune diseases and
hypersensitivity reactions can all cause varying degrees of polyclonal plasmacytosis.
Chronic alcoholism seems to cause a mild plasmacytosis, which occasionally can
increase to the 10% range [personal observation]. In addition, marrow involvement by
plasma cell Castleman Disease may lead to striking marrow plasmacytosis. HIV/AIDS
marrows may also have large numbers of plasma cells. In HIV/AIDS, the plasma cells
may have some morphologic features reminiscent of malignancy. These may be HHV-8
associated plasma cell proliferations and may be precursors to plasma cell malignancies.

Immunophenotype is most helpful in evaluation of plasma cells. Neoplastic plasma cells

will often differ in significant ways from benign. Findings that are present in neoplastic
plasma cells, but not in benign plasma cells include: light chain restriction, more than rare
cells positive for CD20/CD43/CD45, or positivity for CD56, p53 or Cyclin D1. These
findings support a neoplastic diagnosis in a plasma cell proliferation, regardless of the
number of plasma cells present.

Hemophagocytic Syndrome:

Although rare, hemophagocytic syndrome (HPS) in the marrow can both accompany
malignancy and mimic it as well. HPS typically has a poor prognosis. Patients will almost
always have hepatosplenomegaly and cytopenias. There are three circumstances in which
HPS is seen: 1) malignancy-associated 2) infection-associated and 3) idiopathic. In all
cases, there is typically a hypercellular marrow. This increase in cellularity is usually
accomplished by an increase in macrophages/histiocytes. These macrophages will each
individually have varying degrees of internalized hematopoietic cells. Depending on the
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 5/12

stage of the disorder, the macrophages may also contain amorphous debris, and remnants
of hematopoietic components. It is not always easy to distinguish the three types of HPS.
The malignancy-associated type can be seen in conjunction with T-cell lymphomas, B-
cell lymphomas, Hodgkin lymphoma, epithelial malignancies and leukemias, in roughly
that order of frequency. In some situations, especially the T-cell lymphomas, the
malignant cells can be present and quite inconspicuous relative to the background of
hemophagocytosis.

In the circumstance of infection-associated HPS, the infectious agent can be quite varied;
bacterial, fungal, protozoal or viral. In some circumstances, the infectious agent will
either be obviously visible or will be known by history. In most cases of viral infection,
the history is less clear; immunohistochemical stains for viruses may be of great benefit.
As would be expected, the idiopathic group has no identified cause.

The appearance of the marrow can sometime be what I call ‘empty but full’. In these
cases, it appears that there is no residual fat, and all of the marrow space is occupied, but
the cellularity is quite low. The majority of the cellularity is composed of macrophages,
debris and a mixture of inflammatory and stromal elements.

Storage Diseases:

On occasion storage disorders may mimic neoplasms. Most commonly seen are forms of
Neimann-Pick and Gaucher Disease. These can mimic unusual lymphomas or even more
rarely, true histiocytic malignancies. In both of these disorders, marrow macrophages
become filled with metabolic products that build up because of lack of crucial enzymes.
These marrow macrophages will eventually begin to expand in the marrow space. The
degree of involvement may ultimately lead to cytopenias and extramedullary
hematopoiesis because of myelophthisis (marrow replacement).

Histologically, these clusters of macrophages are benign. The cells lack atypical features
and have large amount of cytoplasm. Depending on the product and the staining
technique, they may appear pale and vacuolated.

Hematogones:

Hematogones are immature lymphoid precursor cells. These are more commonly seen in
the bone marrows of children. They are often increased after chemotherapy and in
reactive marrow conditions. When greatly increased, they can be confused with ALL or
possibly lymphoma (Table 3). Hematogones tend to be dispersed throughout the marrow,
not in large clusters. They are usually small, but can be ‘intermediate’-sized, overlapping
the size range of lymphoblasts. They typically have condensed, smudged chromatin, and
only rarely have nucleoli. They have very scant cytoplasm. Their immunophenotype is
similar to B-ALL; hematogones are positive for CD19 and CD10. Using flow or
immunohistochemistry, the differentiation between hematogones and B-ALL can often
be accomplished. Using IHC for CD34 and TdT, markers of precursor cells, hematogones
tend to be more variably positive, while B-ALL is more uniformly positive or negative.
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 6/12

Similar findings are present for CD20 staining. By flow, expression of some surface
immunoglobulin can be seen in a subset of hematogones, but is negative in most ALLs.

Lymphoid Aggregates:

Lymphoid aggregates (LA) are sometimes more difficult to evaluate in marrows. They
are not always pathologic, and their form, location, number and most importantly, the
clinical history, should be evaluated when considering them. LA tend to occur with more
frequency as patients age. Also, they are more common in patients with chronic disease
and autoimmune conditions. Numerous or very large lymphoid aggregates should always
raise a concern for lymphoma. A paratrabecular location of lymphoid aggregates is
suspicious for malignancy, and should be evaluated by immunohistochemical stains. The
composition of the LA is also important. Benign LA are typically composed of
predominantly small lymphocytes, with an intermixture of histiocytes, plasma cells with
only rare larger transformed lymphocytes. Although rare, well-formed germinal centers
can be seen and are more often benign than malignant. If the cellular composition is
homogeneous or there are numerous large lymphocytes, the possibility of lymphoma
should be considered. Benign lymphoid aggregates are typically located adjacent to or
associated with blood vessels. They typically have sharper, more well-defined borders
than lymphoma in marrow.
.
A difficulty in post-treatment marrows is associated with two newer antibody treatments.
Both Rituxan (anti-CD20 antibody) and CAMPATH (anti-CD52 antibody) are used in
the treatment of B-cell lymphomas. Both appear to cause predominantly T-cell LA in
post-treatment marrows. This is further complicated by the fact that many B-cells will
down-regulate CD20 after treatment with anti-CD20 antibodies. In these cases, a
different B-cell stain (CD79a , PAX-5, CD19) should be used to evaluate the composition
of the lymphoid aggregates.
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 7/12

REFERENCES:

Megaloblastic Anemia

Davenport J. Macrocytic anemia. Am Fam Physician, 1996 Jan;53(1):465-468.

Savage DG, Ogundipe A, Allen RH, Stabler SP, Lindenbaum J. Etiology and diagnostic evaluation of
macrocytosis. Am J Med Sci, 2000 Jun;319(6):343-352.

Wickramasinghe SN. The wide spectrum of unresolved issues of megaloblastic anemia. Semin Hematol,
1999 Jan;36(1):3-18.

Hematogones

Davis RE, Longacre TA, Cornbleet PJ. Hematogones in the bone marrow of adults. Immunophenotypic
features, clinical settings, and differential diagnosis. Am J Clin Pathol. 1994 Aug;102(2):202-11.

Longacre TA, Foucar K, Crago S, Chen IM, Griffith B, Dressler L, McConnell TS, Duncan M, Gribble J.
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Rimsza LM, Larson RS, Winter SS, Foucar K, Chong YY, Garner KW, Leith CP. Benign hematogone-rich
lymphoid proliferations can be distinguished from B-lineage acute lymphoblastic leukemia by integration
of morphology, immunophenotype, adhesion molecule expression, and architectural features. Am J Clin
Pathol. 2000 Jul;114(1):66-75.

Plasmacytosis

Gavarotti P, Boccadoro M, Redoglia V, Golzio F, Pileri A. Reactive plasmacytosis. Case report and review
of the literature. Acta Haematol. 1985;73(2):108-10.

Kass L, Kapadia IH. Perivascular plasmacytosis: a light-microscopic and immunohistochemical study of 93

bone marrow biopsies. Acta Haematol. 2001;105(2):57-63.

Nishimoto Y, Iwahashi T, Nishihara T, Katayama H, Kuribayashi K, Takao T, Saito K. Hepatitis-

associated aplastic anemia with systemic plasmacytosis. Acta Pathol Jpn. 1987 Jan;37(1):155-66.

Poje EJ, Soori GS, Weisenburger DD. Systemic polyclonal B-immunoblastic proliferation with marked
peripheral blood and bone marrow plasmacytosis. Am J Clin Pathol. 1992 Aug;98(2):222-6.

Autoimmune Myelofibrosis

Bass RD, Pullarkat V, Feinstein DI, Kaul A, Winberg CD, Brynes RK. Pathology of autoimmune
myelofibrosis. A report of three cases and a review of the literature. Am J Clin Pathol. 2001
Aug;116(2):211-6. Review

Pullarkat V, Bass RD, Gong JZ, Feinstein DI, Brynes RK.

Primary autoimmune myelofibrosis: definition of a distinct clinicopathologic syndrome. Am J Hematol.
2003 Jan;72(1):8-12.

Snyder R. Recent developments in the understanding of benzene toxicity and leukemogenesis. Drug Chem
Toxicol, 200 Feb;21(1):13-25.

Iron in Plasma Cells

Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 8/12

D’Angelo G, Giardini C, Zanco MD. With regards to the presence of iron granules in plasma cells. Recenti
Prog Med, 1991 Dec;82(12):675-676.

Gruzecki AC, Audeh Y, Reddy VV. An unusual finding of plasma cell iron. Arch Pathol Lab Med, 2002
Jul;126(7):873-874.

Mattana RA, Du Plessis L, Stevens K. Iron uptake by plasma cells in hematologic disorders. Acta
Haematol, 1994;92(3):126-129.

Alcohol

Ballard HS. Hematological complications of alcoholism. Alcohol Clin Exp Res, 1989 Oct;13(5):706-720.

Michot F, Gut J. Alcohol-induced bone marrow damage. A bone marrow study in alcohol dependent
individuals. Acta Haematol, 1987;78(4):252-257.

HPS

Allory Y, Challine D, Haioun C, Copie-Bergman C, Delfau-Larue MH, Boucher E, Charlotte F, Fabre M,

Michel M, Gaulard P. Bone marrow involvement in lymphomas with hemophagocytic syndrome at
presentation: a clinicopathologic study of 11 patients in a Western institution. Am J Surg Pathol. 2001
Jul;25(7):865-74.

Florena AM, Iannitto E, Quintini G, Franco V. Bone marrow biopsy in hemophagocytic

syndrome.Virchows Arch. 2002 Oct;441(4):335-44.

Lymphoid Aggregates

Douglas VK, Gordon LI, Goolsby CL, White CA, Peterson LC. Lymphoid aggregates in bone marrow
mimic residual lymphoma after rituximab therapy for non-Hodgkin lymphoma. Am J Clin Pathol. 1999
Dec;112(6):844-53.

Thiele J, Zirbes TK, Kvasnicka HM, Fischer R. Focal lymphoid aggregates (nodules) in bone marrow
biopsies: differentiation between benign hyperplasia and malignant lymphoma--a practical guideline. J Clin
Pathol. 1999 Apr;52(4):294-300.

Vega F, Medeiros LJ, Lang WH, Mansoor A, Bueso-Ramos C, Jones D. The stromal composition of
malignant lymphoid aggregates in bone marrow: variations in architecture and phenotype in different B-cell
tumours. Br J Haematol. 2002 Jun;117(3):569-76.

West RB, Warnke RA, Natkunam Y. The usefulness of immunohistochemistry in the diagnosis of follicular
lymphoma in bone marrow biopsy specimens. Am J Clin Pathol. 2002 Apr;117(4):636-43.

HIV/AIDS

Namiki TS, Boone DC, Meyer PR. A comparison of bone marrow findings in patients with acquired
immunodeficiency syndrome (AIDS) and AIDS related conditions. Hematol Oncol 1987 Apr-Jun;5(2):99-
106.

Godwin JH. HIV/AIDS case histories:diagnostic problems. So-called “bone marrow pattern of AIDS”.
AIDS Patient Care STDS 1999 Jul;13(7):435-6.

Brook MG, Ayles H, Harrison C, Rowntree C, Miller RF. Diagnostic utility of bone marrow sampling in
HIV positive patients. Genitourin Med 1997 Apr;73(2):117-21.
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 9/12

Ricci D, Ponzoni M, Zoldan MC, Germagnoli L, Faravarelli A. Bone marrow biopsy in 50 AIDS patients: a
diagnostic approach. Pathologica 1995 Dec;87(6):640-5.

Kaloutsi V, Kohlmeyer U, Maschek H, et al. Comparison of bone marrow and hematologic findings in
patients with human immunodeficiency virus infection and those with Myelodysplastic syndromes and
infectious diseases. Am J Clin Pathol 1994 Feb;101(2):123-9.

Thiele J, Zirbes TK, Bertsch HP, Titius BR, Lorenzen J, Fischer R. AIDS-related bone marrow lesions –
Myelodysplastic features or predominant inflammatory-reactive changes (HIV-myelopathy)? A
comparative morphometric study by immunohistochemistry with special emphasis on apoptosis and
PCNA-labeling. Anal Cell Pathol 1996 Aug;11(3):141-57.

Thiele J, Zirbes TK, Wiemers P, Lorenzen J, Kvasnicka HM, Fischer R. Incidence of apoptosis in HIV-
myelopathy, Myelodysplastic syndromes and non-specific inflammatory lesions of the bone marrow.
Histopathology 1997 Apr;30(4):307-11.

Katsarou O, Terpos E, Patsouris E, et al. Myelodysplastic features in patients with long-term HIV infection
and Haemophilia. Haemophilia 2001 Jan;7(1):47-52.
.
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 10/12

Table 1. Comparison of Cytokine Effect to AML

Cytokine Leukemia
PB WBC: Left-shift with WBC: Unequivocal
immature forms, rare blasts usually present.
blasts. Toxic granulation. Rare cytoplasmic
No Auer rods. granules (M0-M2, M4-
M5), more granules in
M3. Auer rods
sometimes present
Marrow Hypercellular Hypercellular
M:E RATIO M:E ratio increased Typically increased
Increase in immature Blasts >20%
forms in clusters, but
presence of maturation.
Blasts not typically
increased
IHC Only rare CD34+ or Blasts will often be
CD117+ cells uniformly CD34 + and/or
CD117+

Table 2. Benign versus Malignant Plasmacytosis

Benign Neoplastic
Cytology Atypical features rare Atypical features often
present
CD45/CD43/CD20/CD56 Negative Any or all can be positive
Proliferation (Ki67) <1% +/- increased
P53 Negative Can be positive
Light Chain* Polyclonal Restricted
* Although the single most important criteria, rare light-chain restricted processes can be benign. Very rare
neoplasms may be bi-clonal, and produce both light chains.
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 11/12

Table 3. Comparison of Hematogones with other Lymphoid Processes.

Hematogones Mature ALL
Lymphocytes
CELL SIZE Small- Small Intermediate
intermediate
Chromatin Variable Condensed Blastic
Nuclear contour Round Round-irregular Round-irregular
Nucleoli Rare Not usually seen Common
Cytoplasm Scant Variable; usually Variable
small amount
Arrangement in Small clusters, Scattered Clusters, typically
marrow scattered large
IHC
TdT Few cells + Negative Typically +
CD34 Few cells + Negative Typically +
CD10 Few cells + Negative Positive
CD20 Variable Positive (in B- Negative
cells)
Hematolymphoid Diagnostic Pathways BM Simulators of Malignancy
Dennis O’Malley, MD 12/12

BENIGN BONE MARROW AND SIMULATORS OF MALIGNANCY

CASE HISTORIES:

Case A: Megaloblastic anemia/pernicious anemia

Clinical history: 74 year old female presented with profound weakness and fatigue. Her
CBC results were as follows: WBC: 1.4 x109, hgb 5.3 g/dL, plt 96,000.

Morphologic findings: The bone marrow biopsy is markedly hypercellular. There are
numerous clusters of immature cells with blastic chromatin. The aspirate smear shows
numerous erythroid precursors, including numerous pronormoblasts. There is significant
dyserythropoiesis including nuclear fragmentation, budding and nuclear/cytoplasmic dys-
synchrony. Myeloblasts are not increased.

Case B: Cytokine effect, G-CSF treatment

Clinical history: 32 year old male with a history of AML 2 years previously.

Morphologic findings: The bone marrow is hypercellular. There are numerous immature
appearing myeloid cells on the core biopsy. They do not appear to be myeloblasts, but
there are only rare granulocytes.

Immunohistochemical findings: MPO is strongly positive in the myeloid cells. CD34 is

not increased.

Case C: Polyclonal plasmacytosis

Clinical history: 66 year old male presents with weakness, fatigue. The patient has a
history of alcoholic liver disease and hepatitis C.
Morphologic findings: The bone marrow is hypercellular. Plasma cells comprise 25-30%
of the cellularity. The plasma cell morphology is mature.
Immunohistochemical findings: A CD138 and VS38c confirm the extent of
plasmacytosis. Kappa and lambda immunostains show a polyclonal pattern.

Case D: HIV/AIDS myelopathy

Clinical history: A 34 year old male presents with pancytopenia.

Morphologic findings: The core biopsy is hypercellular. There are increased dysplastic-
appearing megakaryocytes. There is also plasmacytosis and increased lymphocytes, with
some poorly formed lymphoid aggregates.