Morphologically occult systemic mastocytosis in bone marrow: clinicopathologic features and an algorithmic approach to diagnosis.
OBJECTIVE
Bone marrow (BM) biopsy specimens involved by systemic mastocytosis (SM) typically show multifocal, compact, dense aggregates of spindled mast cells (MCs). However, some cases lack aggregate formation and fulfill the World Health Organization 2008 criteria for SM, based on minor criteria.


METHODS
We identified 26 BM cases of KIT D816V-mutated, morphologically occult SM in the BM.


RESULTS
All patients had some combination of allergic/MC activating symptoms. Peripheral blood counts were generally normal. BM aspirates showed 5% or less MCs, which were only occasionally spindled. BM biopsy specimens showed no morphologic classic MC lesions. Tryptase immunohistochemistry (IHC) demonstrated interstitial, individually distributed MCs (up to 5%) with prominent spindling, lacking aggregate formation. MCs coexpressed CD25 by IHC and/or flow cytometry. Spindled MCs constituted more than 25% of total MCs in all cases and more than 50% in 20 of 26 cases.


CONCLUSIONS
Morphologically occult involvement of normal-appearing BM by SM will be missed without appropriate clinical suspicion and pathologic evaluation by tryptase and CD25 IHC and KIT D816V mutation analysis. On the basis of these findings, we propose a cost-effective, data-driven, evidence-based algorithmic approach to the workup of these cases.
From the Divisions of Hematopathology, Reichard.kaaren@mayo.edu.
Kaaren K
KK
Reichard
From the Divisions of Hematopathology.
Dong
D
Chen
Hematology, and.
Animesh
A
Pardanani
Division of Hematopathology, Health Sciences North, Sudbury, Ontario, Canada.
Rebecca F
RF
McClure
From the Divisions of Hematopathology.
Matthew T
MT
Howard
From the Divisions of Hematopathology.
Paul J
PJ
Kurtin
From the Divisions of Hematopathology.
Adam J
AJ
Wood
Laboratory Genetics, Mayo Clinic, Rochester, MN, and.
Rhett P
RP
Ketterling
From the Divisions of Hematopathology.
Rebecca L
RL
King
From the Divisions of Hematopathology.
Rong
R
He
From the Divisions of Hematopathology.
William G
WG
Morice
From the Divisions of Hematopathology.
Curtis A
CA
Hanson
D000328:Adult; D000368:Aged; D000465:Algorithms; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D008297:Male; D008407:Mast Cells / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D053802:Tryptases / Q000378:metabolism; D055815:Young Adult
D053645:Interleukin-2 Receptor alpha Subunit; D019009:Proto-Oncogene Proteins c-kit; D053802:Tryptases
   KIT D816V; Algorithm; Evidence-based medicine; Mast cell activation; Mastocytosis; Test utilization