October 2020 — Hematopathology

The correct answer is POEMS syndrome.

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) diagnosis requires the presence of both mandatory criteria (polyneuropathy plus monoclonal plasma cell disorder), plus at least one major criterion (osteosclerotic bone lesion[s], Castleman disease, or elevated serum or plasma vascular endothelial growth factor levels), in addition to at least one minor criterion (endocrine abnormalities, skin changes, organomegaly, extravascular volume overload, thrombocytosis/polycythemia, and papilledema). The patient in the above vignette presented clinically with lower leg weakness (polyneuropathy), monoclonal plasma cells by flow cytometry, osteosclerotic lesions, diabetes mellitus and erectile dysfunction (endocrine abnormalities), hepatosplenomegaly (organomegaly), lower limb edema and pericardial effusion (volume overload), and thrombocytosis - thus fulfilling the diagnostic criteria of POEMS syndrome. On bone marrow (BM) biopsy and aspirate, most POEMS patients with thrombocytosis present with megakaryocytic hyperplasia that may demonstrate megakaryocytic clustering and cytologic atypia as shown above. Other BM findings that, if present with megakaryocytic hyperplasia, may be present in POEMS syndrome is plasma cell rimming around reactive lymphoid aggregates (not shown above).

Myeloproliferative Neoplasm (MPN) is a clonal hematopoietic stem cell disorder characterized by proliferation of one or more of the myeloid cell lines (erythroid, granulocytic, megakaryocytic). Patients usually have a hypercellular bone marrow with megakaryocytic hyperplasia forming clusters, increased peripheral blood counts (thrombocytosis and/or erythrocytosis) and splenomegaly - a presentation similar to the above case vignette. However, the constellation of clinical symptoms that define POEMS syndrome is absent and the presence of the monoclonal gammopathy and clonal plasma cell population are not seen in MPNs. Molecular testing for mutations associated with MPNs (JAK2, CALR, MPL) will be negative in POEMS syndrome in spite of the BM morphology.

Plasma cell myeloma patients usually present with renal insufficiency, hypercalcemia, osteolytic bone lesions (not sclerotic changes), anemia, pathologic fractures, and a >10% plasma cells in the bone marrow along with a monoclonal protein in the serum and/or urine. Megakaryocytic hyperplasia and clustering is not a feature seen on bone marrow biopsy in standard myeloma patients.

Waldenström macroglobulinemia (WM) is lymphoplasmacytic lymphoma with the presence of an IgM monoclonal gammopathy. Patients may have signs and symptoms related to the high IgM levels including hyperviscosity syndrome (blurring or loss of vision, headache, vertigo, etc.), neuropathy, cryoglobulinemia and renal insufficiency. In contrast, patients with POEMS syndrome present with polyneuropathy, monoclonal plasma cell disorder, and other constellation of clinical symptoms (see major and minor criteria in A). Bone marrow and/or lymph node biopsies in WM usually have abnormal lymphoplasmacytic infiltrates. These abnormal cellular infiltrates, along with absence of other the clinical criterion for POEMS syndrome distinguishes both entities.

Solitary plasmacytoma of bone (SPB) patients have a single osteolytic bone lesion, whereas patients with POEMS syndrome usually have multiple osteosclerotic lesions. In addition, the presence of other clinical criterion in POEMS syndrome should help distinguish between these two entities.

References
1. Dao LN, Hanson CA, Dispenzieri A, Morice WG, Kurtin PJ, Hoyer JD. Bone marrow histopathology in POEMS syndrome: a distinctive combination of plasma cell, lymphoid, and myeloid findings in 87 patients. Blood. 2011;117(24):6438-6444. doi:10.1182/blood-2010-11-316935
2. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548. doi:10.1016/S1470-2045(14)70442-5
3. Rajkumar SV. POEMS syndrome. UpToDate. Retrieved July 22 2020 from https://www.uptodate.com/contents/poems-syndrome
4. Tefferi A, Pardanani A. Myeloproliferative Neoplasms: A Contemporary Review. JAMA Oncol. 2015;1(1):97-105. doi:10.1001/jamaoncol.2015.89
5. Soutar R, Lucraft H, Jackson G, et al. Guidelines on the diagnosis and management of solitary plasmacytoma of bone and solitary extramedullary plasmacytoma. Br J Haematol 2004; 124:717.
6. Dimopoulos MA, Panayiotidis P, Moulopoulos LA, Sfikakis P, Dalakas M. Waldenström's macroglobulinemia: clinical features, complications, and management. J Clin Oncol. 2000;18(1):214-226. doi:10.1200/JCO.2000.18.1.214