A cachectic 78 year old woman presented with hepatosplenomegaly,
axillary lymphadenopathy and a 20-30 pound weight loss over a one year
period. She was anemic and thrombocytopenic. There was a leukocytosis
with an absolute monocytosis, and neutrophilia. Qualitative peripheral
blood abnormalities included: dysmyelopoiesis, slight
hypersegmentation, slight micro- and macro-cytosis, NRBCs in the
peripheral blood, and large platelets.
The past medical history included a bone marrow aspirate/biopsy
performed at an outside hospital which demonstrated 90% cellularity
with an increased M:E ratio due to increased immature myeloid elements.
The marrow was suspicious for CML vs. myelofibrosis. At this time, the
WBC was 33.5; Hct 32; Plt 125K. Despite a LAP of 23, CML was considered
the working diagnosis. No treatment was required. Shortly before
diagnostic bone marrow biopsy was performed FNA of an axillary LN
showed extramedullary hematopoiesis.
||(12 - 16)
||(35 - 57)
||(83 - 95)
||(40 - 82)
||(15 - 45)
||(2 - 12)
||(0 - 6)
||(0 - 0.2)
||(less than 4.0)
||(1 - 5)
||(0 - 1)
||(0 - 0.6)
||(0 - 0.2)
Qualitative PB Abnormalities: WBC: Moderate left shift with
increased bands, metamyelocytes, myelocytes, rare promyelocyte, and
dysmyelopoiesis. RBC: Marked anisocytosis and occasional
A diagnostic bone marrow biopsy was performed:
The bone marrow cellularity was 100% with a predominance of
Leder-positive granulocytic elements and several abnormal
paratrabecular aggregates of mast cells. The myeloid:erythroid ratio
was greatly increased due to the extensive proliferation of myeloid
elements demonstrating a full range of maturation. Prominent nuclear
sticks suggested mild dysmyelopoiesis. Scattered normal-appearing
erythroid and megakaryocytic elements were present.
Most striking were the multiple paratrabecular aggregates of
Leder-positive oval and spindle-shaped mast cells, many with atypical
folded or indented nuclei. Toluidine blue staining showed metachromatic
granulation. Fibrosis within these aggregates was demonstrated by
reticulin and trichrome staining. Some aggregates were partially
surrounded at the periphery by lymphocytes and eosinophils. Only small
numbers of lymphocytes, plasma cells, and eosinophils were present
within the mast cell aggregates. The findings of a hypercellular marrow
with a predominance of myeloid elements, minimal dysmyelopoiesis, and
dyserythropoiesis, and abnormal paratrabecular mast cell aggregates,
support the morphologic impression of a chronic myeloproliferative
disorder involving mast cells.
As reported in the literature, this patient presents with a
classical picture of systemic mast cell disease*. The bone marrow
findings are consistent with systemic mast cell disease type 2, also
known as malignant mastocytosis*. The systemic mast cell disorders are
clinically defined by some or all of the following: anemia,
thrombocytopenia, monocytosis, leukocytosis with increased neutrophils,
qualitative peripheral smear changes, increased serum alkaline
phosphatase, LDH, and histamine, and the physical findings of
hepatosplenomegaly and lymphadenopathy.
Based on bone marrow histopathology, systemic mast cell diseases
have been divided into three types*.
Type 1 (Benign Systemic Mastocytosis) generally involves the skin as
well as the reticuloendothelial system. Type 1 is characterized by
paratrabecular aggregates of mast cells accompanied by dense reticulin,
thickening of the adjacent bony trabeculae, and increased lymphocytes
and plasma cells within the aggregates. A rim of increased eosinophils
often surrounds the aggregates. The non-infiltrated marrow fat and
hematopoeisis are normal. The clinical outcome of Type 1 mast cell
disease is generally favorable with survival averaging 10 years or
Type 2 disease (Malignant Mastocytosis) typically demonstrates in
addition to the marrow findings seen with Type 1 disease, marked
fibrosis and osteosclerosis, but does not usually demonstrate increased
lymphocytes and plasma cells within the mast cell aggregates. The
non-mast cell infiltrated marrow shows decreased fat content and
increased granulocytopoiesis or myeloid blast cells.
Type 3 disease (Malignant Mastocytosis) is characterized by diffuse
marrow infiltration with atypical mast cells, hypoplasia of the marrow
hematopoietic cells, and may demonstrate mast cell leukemia. The
prognosis of type 2 and type 3 disease is poor with survival periods
usually no more than 1-2 years.
Although flow cytometric immunotyping was not available for this
case, a recent report shows that multiparametric flow cytometry of bone
marrow can be useful in distinguishing indolent systemic mast cell
disease (CD2+; CD 25+; CD 35+; CD 71-) from reactive mastocytosis
(CD2-; CD 25-; CD 35-; CD 71+).
|CD 2 +
||CD 2 -
|CD 25 +
||CD 25 -
|CD 35 +
||CD 35 -
|CD 71 -
||CD 71 +
Systemic Mast Cell Disease, Type 2 (Malignant Mastocytosis)
Escribano, L, et. al. Indolent Systemic Mast Cell Disease in Adults:
Immunophenotypic Characterization of Bone Marrow Mast Cells and Its
Diagnostic Implications. Blood 91(8):2731-2736, 1998.
*Horny, H.P., Parwaresch, M.R., and Lennert, K. Bone Marrow Findings
in Systemic Mastocytosis. Hum. Path. 16(8):808-814, 1985.
Horny, H.P., et. al. Immunoreactivity of Normal and Neoplastic
Tissue Mast Cells. A.J.C.P. 89(3):335-340, 1988.
Horny, H.P. et. al. Immunoreactivity of Normal and Neoplastic Human
Tissue Mast Cells with Macrophage-Associated Antibodies, with Special
Reference to the Recently Developed Monoclonal Antibody PG-M1. Hum.
Path. 24(4):355-358, 1993.
Lawrence, J.B. et. al. Hematological Manifestations of Systemic Mast
Cell Disease: A Prospective Study of Laboratory and Morphologic
Features and Their Relation to Prognosis. Am. J.Med., 91:612-624,
Torrey, E. et. al. Malignant Mastocytosis With Circulating Mast
Cells. Am. J. Hematology. 34:283-286, 1990.
Travis, WD, et.al. Systemic Mast Cell Disease: Analysis of 58 Cases
and Literature Review. Medicine (Baltimore). 67:345-368, 1988.
Travis, W.D. and Li, C.Y. Pathology of Lymph Node and Spleen in
Systemic Mast Cell Disease. Mod. Path. 1(1):4-14, 1988.
William E. Field II, M.D.
Department of Pathology
University of Virginia Health System.
Donald J. Innes, Jr., M.D.
Department of Pathology
University of Virginia Health System
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