Bone Marrow (BM) Histopathology of POEMS Syndrome: Analysis of 134 Cases Reveals Features Which May Obscure the Diagnosis and Mimic a Myeloproliferative Neoplasm (MPN)
LD Dao, WG Morice, PJ Kurtin, A Dispenzieri, JD Hoyer. Mayo Clinic, Rochester, MN
Background: POEMS is a rare syndrome comprised of polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell (PC) dyscrasia, skin changes, sclerotic bone lesions, Castleman disease (CD), edema, papilledema and thrombocytosis. The BM histopathology of POEMS remains poorly characterized.
Design: Peripheral blood (PB) smears, BM aspirates and biopsies from 137 clinically documented POEMS cases were reviewed. PC clonality was analyzed by 2 or 6 color flow cytometry (FC) (100 and 37 cases respectively), BM immunohistochemistry (IHC) (66 cases) and in situ hybridization (3 cases). JAK2 mutational analysis was performed on 43 BM aspirates or PBs.
Results: Table 1 summarizes the clinical, PB and BM findings. Megakaryocyte hyperplasia and clusters were frequent, however none of the POEMS cases tested had detectable JAK2 mutation. Erythroid and granulocytic dysplasia was not present. Lymphoid aggregates (LA) were also common and in most cases were surrounded at the periphery by PCs. One case had diagnostic features of CD. Monotypic PCs were detected in 62 cases (45%) by either IHC and/or FC; the vast majority of monotypic PCs expressed light chain. The monotypic PCs were typically present in a background of polytypic PCs, and in many cases only polytypic PCs were identified.
Table 1: Clinical, PB and BM findings
|# of cases (%)|
|Hypercellular for age||28 (20)|
|Megakaryocyte hyperplasia||47 (34)|
|Megakaryocyte clustering||No clusters||30 (22)|
|1-4 clusters||75 (55)|
|5+ clusters||32 (23)|
|Megakaryocyte cytology||Large||28 (20)|
|Lymphoid aggregate||49 (36)|
|PC rimming||42/49 (86)|
|Monotypic ||59 (43)|
|Monotypic ||3 (2)|
|Too few PC (by FC)||3 (2)|
Conclusions: The BM histopathology of POEMS is complex with features which may be associated with other disorders. For example, many of the features may evoke a suspicion of a MPN. Likewise the PC clonality of POEMS may be difficult to detect due to the presence of a polytypic PC background. The PC-rimmed LAs are distinctive. POEMS should be considered when these unusual features are encountered in the setting of monoclonal gammopathy and/or unexplained neuropathy.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 178, Monday Morning