Dr. Paul Mellor, DECVIM
In our series, cytological and histopathological sections were categorized according to an adaptation of the method described by Wutke et al. (Wutke et al 1981, Mellor et al 2008). Myeloma cells were classified as mature myeloma cells, proplasmacytes, plasmablasts, giant myeloma cells or lymphoid (see figures below). Tumours were then categorized on the basis of the proportion of plasmablasts: (see Table below). Overall, there was good concordance between cytology and histopathology in the morphological categorization of MRD in our series, as has been reported in human myeloma patients (Wutke et al 1981, Thiry et al 1993).
Categorization of MRD by proportion of plasmablasts:
| Tumour Category | Tumour description |
| 1. Well-differentiated MRD | <15% plasmablasts. Remainder mature myeloma cells or proplasmacytes or lymphocytes. |
| 2. Intermediate-grade MRD | 15-49% plasmablasts. Remainder mature myeloma cells or proplasmacytes or lymphocytes. |
| 3. Poorly-differentiated MRD | >50% plasmablasts. Remainder mature myeloma cells or proplasmacytes or lymphocytes. |
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Fig 1a: Mature myeloma cells - cytological appearance. These are cclassical, terminally-differentiated neoplastic plasma cells (Marschalko cells) and have an eccentrically located round-to-oval nucleus that is typically 1 - 1.5 times the diameter of a red blood cell. There is minimal anisokaryosis. The nucleus has a dense chromatin pattern and no nucleoli. Cytoplasmic appearance varies:- (i) abundant highly basophilic cytoplasm and a perinuclear clear zone (examples seen in Fig 1) ii) “Flame” cells - large amounts of eosinophilic staining material that may be confined within one large vacuole, or spread throughout the cytoplasm, or spill out beyond the cell membrane forming an eosinophilic halo around the cell. iii) Mott / Russell body cells - multiple intracytoplasmic vacuoles (grape-like accumulations that may be clear, basophilic or eosinophilic) within the cytoplasm. May-Grünwald-Giemsa stain. X1000 total magnification. (Mellor et al 2008) (Copyright Veterinary Pathology). |
Fig. 1b: Mature myeloma cells - histopathological appearance. See cytological description, except the cytoplasm appears eosinophilic. Flame cells and Mott cells may also be seen. Chromatin clumping gives rise to a “clock face” or “cartwheel” appearance. The nucleolus may be indistinct or small. HE. X400 total magnification. (Mellor et al 2008) (Copyright Veterinary Pathology). |
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Fig. 2a: Proplasmacytes - cytological appearance. Proplasmacytes are larger than mature myeloma cells, show greater anisocytosis and display asynchronous nuclear and cytoplasmic maturation. They have an eccentrically located large nucleus (round, ovoid, indented or sickle-shaped) containing indistinct or small nucleoli. Cytoplasmic appearance varies (see description of mature myeloma cells). May-Grünwald-Giemsa stain. X1000 total magnification. (Mellor et al 2008) (Copyright Veterinary Pathology). |
Fig. 2b: Proplasmacytes - histopathological appearance. See cytological description, except cytoplasmic appearance varies from eosinophilic to the categories defined in the cytological description of mature myeloma cells. HE. X400 total magnification. (Mellor et al 2008) (Copyright Veterinary Pathology). |
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Fig. 3a: Plasmablasts - cytological appearance. Plasmablasts are larger than mature myeloma cells and show greater anisocytosis. They have a small rim of basophilic cytoplasm, and a less distinct or inapparent peri-nuclear clear zone. Cytoplasmic inclusions (see description of mature myeloma cells) may be seen in some cells. They have a high N:C ratio, a large and immature, round to ovoid, eccentrically located nucleus with anisokaryosis and ?1 prominent nucleoli. May-Grünwald-Giemsa stain. X1000 total magnification. (Mellor et al 2008) (Copyright Veterinary Pathology). |
Fig. 3b: Plasmablasts - histopathological appearance. See cytological description, except the eccentrically located nucleus was generally ovoid with ?1 prominent nucleoli. HE. X400 total magnification. (Mellor et al 2008) (Copyright Veterinary Pathology). |
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Fig. 4a: Giant myeloma cells - cytological appearance. Skin mass. Giant myeloma cells can be mistaken for megakaryocytes, but are seen in atypical sites i.e. they are noted outside of the bone marrow or typical sites of extra-medullary haematopoesis. May-Grünwald-Giemsa stain. X1000 total magnification. (Mellor et al 2008) (Copyright Veterinary Pathology). |
Fig. 4b: Giant myeloma cells - histopathological appearance. Skin mass. HE. X1000 total magnification. (Mellor et al 2008) (Copyright Veterinary Pathology). |
| Fig. 5: Immunoglobulin secreting lymphoma (HE) - Lymphoma cells typically have less basophilic cytoplasm, no peri-nuclear clear zone, a higher n:c ratio with a round and centrally located nucleus. Lymphoma was allowable in the diagnosis of a MRD, so long as the patient also had hyperglobulinaemia (total serum globulin >52g/L) attributable to a M-proteinaemia, as evidenced by serum protein electrophoresis. Lymphoma may be classified according to the NCI WF scheme (Valli et al 2000). In this case, the diagnosis was small cell lymphoma with hepatic, intestinal, mesenteric lymph node and marrow involvement. Biopsies taken at initial presentation showed mixed CD79a+ and CD3+ expression with absence of Ig labelling despite hyperglobulinaemia and paraproteinaemia (Mellor et al 2008).
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