Plasma cell myeloma

Ingestion of haemopoietic cells can be found in some cases of plasma cell leukaemia or plasma cell myeloma. A band neutrophil was ingested by a binuclear myeloma cell (green arrow), whereas another tumour cell contains an ingested erythrocyte (red arrow).

A tumour cell can also ingest another tumour cell (green arrow). Pathological plasma cells contain numerous Russell bodies in their cytoplasm (yellow arrows). The “rouleaux” formation of erythrocytes is evident in the smear (red arrow).

Numerous Russell bodies can be found in some tumour cells (green arrow, red arrow); when Russell bodies or apparent vacuoles almost fill up the cytoplasm content, the cell is referred to as the “Mott cell” (red arrow). A Russell body must be distinguished from an ingested erythrocyte (yellow arrow).

Myeloma plasma cells and a multinucleated cell (red arrow). Note the prominent anisocytosis, marked basophilia and minute vacuoles in the cytoplasm of the cells.

Small pathological plasma cells with basophilic villous cytoplasm and off-centre located nuclei.

Basophilic plasma cells and one plasma cell with a double nucleus (red arrow). Note the deeply basophilic cytoplasm without perinuclear halo.

A medium-sized plasma cell (red arrow) with needle-shaped cytoplasmic inclusions.

Marshall cells with a prominent perinuclear halo, eccentrically located nuclei without nucleoli and a relatively dense structure of nuclei. Note the marked rouleaux formation of erythrocytes, which is caused by the presence of paraprotein.

Mott cells: the cytoplasm of these bizarre plasma cells is packed with Russel bodies of a variable size.

One plasma cell with a huge cytoplasmic inclusion – the Russel body – in the cytoplasm (yellow arrow). The pinkish colour of the inclusion is caused by IgA paraprotein.

This image shows lymphoplasmacytoid cells, i.e. lymphoid elements with features of plasma cells (e.g. rich in basophilic cytoplasm).

Pleomorphic myeloma plasma cells of “monocytoid” type with a fine structure of nuclei and rare nucleoli. Note the giant multi-nucleated element (red arrow).

Giant myeloma plasma cells containing large nuclei with fine chromatin and visible nucleoli. The characteristic perinuclear halo is lacking.

Large multinucleated myeloma plasma cell featuring fine nuclear chromatin and prominent nucleoli. The cytoplasm is deeply basophilic with fine inclusions.

Myeloma plasma cells with prominent anisocytosis and relatively small nuclei. Note the marginal carminophilia of cytoplasm, which is rather marked in this case.

The current widely accepted model of plasma cell myeloma oncogenesis describes two different pathways. The first one is represented by hyperdiploidy, which is observed in up to 55% of patients, whereas the second one is based on IGH translocations, which are observed in approximately 40% to 50% of patients. Hyperdiploidy is characterised by trisomies of certain odd-numbered chromosomes, namely, 3, 5, 7, 9, 11, 15, 19, and 21. Non-hyperdiploidy plasma cell myeloma involves translocations of immunoglobulin heavy chain locus (IGH) at chromosome 14q32 with various partner chromosomes as chromosomes 4, 6, 11, 16, and 20. Besides these supposedly primary events, many other chromosomal rearrangements are present in tumour plasma cells at the time of diagnosis. The most frequent ones involve monosomy 13 (45%), duplication of the long arm of chromosome 1 (1q gains, 30% to 35%) and various deletions, involving mainly chromosomal regions 1p and 17p.

• A, B: Chromosome 1 abnormalities are found in almost 50% of cases of plasma cell myeloma. Gain of the chromosome 1q arm (Fig. A) is frequently observed along with loss of the 1p32 region (Fig. B). The orange-labelled probe hybridises to a specific region at 1q21 (CKS1B gene), whereas the green-labelled probe hybridises specifically to 1p32 (CDKN2C gene). A locus-specific dual colour FISH probe was used.
• C: Chromosome 17p deletion is detected in 10% of newly diagnosed cases of plasma cell myeloma, but its prevalence increases in later stages of the disease. The deletion 17p includes tumour suppressor gene TP53 located at 17p13. The specific probe covering the TP53 gene is labelled in orange, whereas a green-labelled probe, which hybridises to the centromere of chromosome 17, functions as a reference probe. A locus-specific FISH probe was used.
• D: Chromosome 13 deletion is observed in 45% of cases of plasma cell myeloma (in approximately 85% of these cases as a a monosomy or loss of the q arm, and in approximately 15% of these cases as interstitial deletions). The orange-labelled probe hybridises to the DLEU locus region at 13q14.2, whereas the green-labelled probe hybridises to the RB1 gene region at 13q14.2. A blue-labelled probe hybridises to the LAMP gene locus at 13q34. A locus-specific FISH probe was used.

Translocations involving the immunoglobulin heavy chain locus (IGH) at chromosome 14q32 are observed in approximately 40% to 50% of all cases of plasma cell myeloma. The most important partner chromosomes are chromosomes 4, 6, 11, 16, and 20.

• A: Translocations of IGH region were detected by a break-apart FISH probe. Its orange-labelled part hybridises to the constant region of the IGH locus, whereas the green-labelled probe hybridises to the variable distal region of the IGH locus. A typical IGH translocation pattern involves one green-orange fusion signal (yellow arrow) and two separate signals (1 orange and 1 green), indicating a chromosome break in the IGH locus.
• B: The translocation t(11;14)(q13;q32) was detected by a dual-colour dual-fusion FISH probe. In this translocation, which is present in 15% of cases, the CCND1 proto-oncogene at 11q13 is juxtaposed to the IGH gene, resulting in an overexpression of the protein product, cyclin D1. A typical t(11;14) pattern involves two separate signals (one orange and one green) and two green-orange fusion signals (yellow arrows), indicating t(11;14)(q13;q23).
• C: The translocation t(4;14)(p16;q32) was detected by a dual-colour dual-fusion FISH probe. This translocation is present in approximately 15% of primary plasma cell myelomas and results in an overexpression of two proto-oncogenes, FGFR3 and MMSET, by juxtaposition next to the IGH enhancers. A typical t(4;14) pattern involves two separate signals (one orange and one green) and two green-orange fusion signals (yellow arrows), indicating t(4;14)(p16;q23).
• D: The translocation t(14;16)(q32;q23) was detected by a dual-colour dual-fusion FISH probe. The translocation t(14;16) is found in 3–7% of all plasma cell myelomas and results in an overexpression of the c-MAF proto-oncogene. A typical t(14;16) pattern involves two separate signals (one orange and one green) and two green-orange fusion signals (yellow arrows), indicating t(14;16)(q32;q23).

Plasma cell myeloma. Diffuse infiltration of bone marrow. The tumour is composed of mature-appearing (“Marschalkó-type”) plasma cells with a low nuclear-cytoplasmic ratio, eccentric nuclei with clumped chromatin, and perinuclear pale Golgi zone in the cytoplasm. There is no mitotic activity: in this case, the proliferation index measured by Ki67 was below 1%.

Osteolytic lesion of vertebra, biopsy, haematoxylin and eosin stain.

Plasma cell myeloma. Diffuse infiltration of bone marrow. This tumour is composed of immature plasma cells with a slightly increased nuclear-cytoplasmic ratio, nuclear-cytoplasmic asynchrony and conspicuous nucleoli. In this case, the proliferation index measured by Ki67 was more than 35%.

Osteolytic lesion of vertebra, biopsy, haematoxylin and eosin stain.

Plasma cell myeloma. Tumour cells show strong membrane positivity for CD138 (syndecan-1). 

Osteolytic lesion of vertebra, biopsy, immunohistochemistry.

Plasma cell myeloma. Tumour cells show strong cytoplasmic positivity for kappa immunoglobulin light chains. The lambda light chains were completely negative.

Osteolytic lesion of vertebra, biopsy, immunohistochemistry.