Open Journal of Pathology, 2012, 2, 127-132
Published Online October 2012 (http://www.SciRP.org/journal/ojpathology)
http://dx.doi.org/10.4236/ojpathology.2012.24023
127
Plasma Cell Neoplasms, Clinicopathological
Characteristics and Immunophenotype of 21 Patients
Mónica Belinda Romero-Guadarrama1,2*, Cinthia Adriana Meza Medina3, Elvira Aguilar Martínez4
1Unidad de Patología del Hospital General de México, Mexico City, Mexico; 2Facultad de Medicina, Universidad Nacional
Autónoma de México, Mexico City, Mexico; 3Facultad de Medicina, Universidad Autónoma de Nayarit, Tepic, Mexico; 4Unidad de
Hematología del Hospital General de México, Mexico City, Mexico.
Received August 9th, 2012; revised September 9th, 2012; accepted September 19th, 2012
ABSTRACT
Introduction: Plasma cell neoplasms are monoclonal proliferations characterized by the secretion of an immunoglobu-
lin product known as component “M” or monoclonal. The World Health Organization (WHO 2008) defines as plasma
cell neoplasms the following: plasma cell myeloma, plasmacytoma and those syndromes defined by immunoglobulin
deposits and primary amyloidosis, The objective of the present work was to correlate their clinical, morphological and
phenotype characteristics in 21 patients. Material and Methods: A 2-year retrospective review was performed of the
files of the surgical pathology laboratory and of the hematology service of the General Hospital of Mexico, searching
for patients with a diagnosis of plasma cell neoplasm. We analyzed the following variables: age, gender, clinical symp-
toms, evolution, localization, laboratory tests, morphology, and expression of immunohistochemical markers. Of the 21
patients, 12 (57.1%) corresponded to plasma cell myelomas and 9 (42.8%) were plasmacytomas (seven extraosseous
and two solitary bone plasmacytoma); women predominated with 61.4% and ag e ranged b etween 22 and 84 years. Mass
and epistaxis were observed in the patients with plasmacyto mas, and sympto ms of me dulla ry compr ession and anemia
were observed in those patients with plasma cell myeloma. The time of symptomatology varied from 3 to 12 months.
Laboratory tests revealed that lactate dehydrogenase (LDH), beta 2 microglobulin, C-reactive protein were altered and
that hypercalcemia and anemia were present more in the systemic form of the disease. Treatment depended on the
clinical staging and laboratory data. Mature fo rms predominated morphologically. Immunohistochemical stain revealed
a constant expression for CD 138, six patients expressed CD 56, and expression of the Kappa and Lambda light chains
was while.
Keywords: Plasma Cell Neoplasms
1. Introduction
Clonal proliferations of plasmatic cells and their precur-
sors constitute a spectrum of diseases previously known
as: “plasma cell dyscrasias”. This group includes mono-
clonal gammopathy of indeterminate significance, which
is characterized by the presence of low levels of para-
protein in the peripheral blood, with a variable time of
evolution, and later on development of a plasma cells
myeloma; this phenomenon is considered as a precursor
lesion.
Other immunoglobulin secreting neoplasms that affect
lymphoid and plasmatic cells lie within the current clas-
sification of WHO-2008 regarding hematolymphoid neo-
plasms, such as the lymphoplasmacytic lymphoma, W ald-
enström’s macroglobulinemia, and heavy chain diseases
[1].
A myeloma is a disease of adults with an average age
of 62 years, it manifests by bone pain, lithic injuries in
several bones, anemia, and recurring infections. It was
first described in 1844 by Dr. Samuel Solly, who as-
signed the name Mollities ossium to the condition [2]. Dr
Bence Jones studied urine samples and described the
proteins that bear his name (BJ) [3]. It was in 1873 that
Rustizky described and used for the first time the term
“multiple myeloma” to point out the variety of bone le-
sions [4].
The solitary bone plasmacytoma affects the axial
skeleton and the thoracic vertebras, it is manifested by
localized bone pain and medullary compression symp-
toms; 70% of patients present systemic symptoms after 2
to 4 years of evolution [5]. The extramedullary plas-
macytoma is localized in the head and neck, gastrointes-
tinal tract, central nervous system, skin, and other organs.
In general, it does not produce detectable serum parapro-
*Corresponding a uthor.

Plasma Cell Neoplasms, Clinicopathological Characteristics and Immunophenotype of 21 Patients 128
teins and rarely becomes disseminated. The diagnosis of
solitary bone plasmacytoma or extraosseous myeloma is
established after extensive imaging studies, such as MRI
to exclude systemic disease. The risk of local recurrence
and dissemination is high in patients with solitary bone
plasmacytoma accompanied by persistence of mono-
clonal serum protein after local radiothera phy [5].
The objective of this study is to present the clinical,
morphological, and immunophenotype characteristics of
21 patients studied at the General Hospital of Mexico.
2. Material and Methods
From the archives of the Surgical Pathology and Immu-
nohistochemistry Service of the Pathology Unit of the
General Hospital of Mexico, we reviewed the slides
stained with hematoxylin-eosin, periodic acid-Shiff stain
and the immunohistochemical markers of 21 patients
diagnosed with plasma cell neoplasms and classified
them according to WHO-2008 guidelines for hema-
tolymphoid neoplasms [1] diagnosed in a two-year pe-
riod (2006 and 2007).
We identified the morphology of the plasmatic cells:
mature, lymphoplasmacytic and immature or anaplastic.
Strepto-avidin-biotin-peroxidase was the immunohisto-
chemical technique used manually. The monoclonal an-
tibodies used were: Kappa (1:1000), Lambda (1:1000),
CD 138 (1:50), CD 56 (1:20), CD 20 (1:50) and CD5
(1:50) (D ako, Carpi nt e ir a, CA, USA).
Clinical information was gathered from the clinical
files and we analyzed the following variables: age, gen-
der, localization, duration of symptoms, and laboratory
tests performed, anemia, lactate dehydrogenase (LDH),
beta-2-microglobulin, and serum proteins. We correlated
the clinical morphological variables and the immuno-
phenotype.
3. Results
From the 21 patients with a diagnosis of plasma cell neo-
plasm, 12 were identified with having plasma cell mye-
lomas (M) and 9 had plasmacytomas (7 extraosseous and
2 osseous ) (P) (Figure 1).
The clinical data of the patients with plasma cell mye-
loma (57.7%) are depicted on Table 1 . Nine (75%) were
women and three (25%) were men.
The youngest patient was a 31-year-old woman, who
at the time of diagnosis presented a 38-week pregnancy.
The oldest was a man of 84 years. Average age was 54.2
years. The most affected sites were the skull in six (50%),
spinal cord in 4 (33.3%), and less frequently affected
structures were bone marrow, long bones, pelvis, clavicle,
palate, lymph node, and intestine.
Figure 1. Plasmacytoma in the antrochoanal región.
Table 1. Clinico-pathological characteristics of patients with plasma cells myeloma.
Case Gender Age Site Laboratory Morphology Inmunohistochemistry
1 w 42 Skull and thorax B-2m MPC CD 138/Kappa
2 m 52 SC T5 and T4 Anemia, LDH MPC CD 138/Kappa
3 w 59 Palate, skull Anemia, LDH Sx viscocity ARF, GammopathyMPC CD 138/Kappa
4 w 65 Skull Intestine LN, BM, Anemia, B2-m PB J+ MPC CD 138/Kappa
5 w 43 SCT2 LN Lumbar pain Anemia, IgG/K Gammopathy IPC CD 138/Kappa CD 56+
6 w 50 Thorax, clavicle Humer (PF) Anemia, B-2m ARF MPC CD 138/Kappa
7 w 56
Parietal skull BM, pain in half of
the face infiltrated BM B-2m, FRA MPC CD 138/Lambda
8 w 66 SC C T BM PBJ+ Anemia MPC CD 138/Lambda CD 56+
9 m 56 SCT Pain, paresthesias B-2m MPC CD 138/Lambda
10 w 31 Scapula Pelvis PF B-2m, FRA Preg 38WG IPC CD 138/Lamb da
11 w 47 Skull and long bones Anemia, PB J+ B-2m MPC CD 138/Lambda
12 m 84 Skull and pelvis Bone pain Anemia LDH MPC CD 138/Lambda
B-2m (Beta-2 microglobulin), LDH (Lactic dehidrogenase), ARF (Altered renal function), PBJ (Bence-Jones Protein), Preg (pregnancy) WG (weeks of gesta-
tion), MPC ( mature plasma cells), IPC (immature plasma cells), PF (pathological fracture). VC (vertebral column), BM (bone marrow), LN (lymph node ).

Plasma Cell Neoplasms, Clinicopathological Characteristics and Immunophenotype of 21 Patients 129
Seven patients (58.3%) presented anemia, in six (50%)
2-beta-microglobulin of more than 3.5 mg/L was found,
three patients presented monoclonal gammopathy: IgG >
3.5 g/dL, IgA > 2 g/dL, and two patients had altered re-
nal function, one coursed with hypercalcemia and ele-
vated LDH.
Morphologically, the neoplastic cells corresponded to
mature plasmatic cells in 10 patients (83.3%) (Figure 2)
and two showed immature and pleomorphic plasmatic
cells (Figure 3). The determined immunohistochemical
markers are summarized in Table 1, in which expression
for CD138 was observed (Figure 4); 6 patients (50%)
expressed light Kappa chain and 50% Lambda (Figures
5 and 6 respectively). Two patients (16%) expressed CD
Figure 2. Mature plasma cells neoplasm (myeloma), in
which cells depict and eosinophil cytoplasm and an eccen-
tric nucleus. Some cells show cytoplasmic immunoglobulins
(H-E).
Figure 3. Plasma cells neoplasm with immature morphology.
Note the pleomorphism of cells (H-E).
Figure 4. Inmunohistoche mistry, note CD 138 expression in
the cytoplasms of neoplastic plasma cells.
Figure 5. Lambda expression can be observed in most neo-
plastic cells, Immunohistochemi c al r eaction.
Figure 6. Note the lack of Kappa expression. Immunohisto-
chemical reaction.

Plasma Cell Neoplasms, Clinicopathological Characteristics and Immunophenotype of 21 Patients 130
56, which morphologically corresponded to mature plas-
ma cells and the other presented immature cells (Table
1), The others markers such CD 20 and CD 5 were nega-
tive.
The Table 2 depicts the clinical data of patients with
plasmacytomas (9 cases, 42.8%). Seven were extraosse-
ous (77.7%) and two were bone (33.3%). Four patients
were men and five women, the youngest patient was a
22-year-old man without HIV antecedents and the loca-
tion was in a lymph node associated to Castleman’s dis-
ease, hyaline vascular type. The oldest patient was a
79-ye ar-old patien t, and the av erage ag e was of 52 years.
The sites of the extraosseous plasmacytomas were: two
in the nasal region and two more in the palate, an d one in
the following sites, anthrocoanal, gum, and cervical
lymph node. The bone plasmacytomas were found in
cervical vertebra and the sternum. Morphologically, seven
were constituted by mature plasma cells and two re-
vealed the presence of lymphocytes and plasmatic cells
(lymphoplasmacytic variant). Immuno histochemical pat-
terns in five expressed Kappa and two Lambda; expres-
sion for CD 56 was observed in four (44.4%). The others
markers such CD 20 and CD 5 were negative (Table 2).
4. Discussion
According to the compiled Histopathological Registry of
1997, plasma cell tumors occupied the 15th place and
corresponded to less than 1% (0.4%) of the total malign-
nant neoplasms in our country [6].
At the Instituto Nacional de Cancerología [National
Cancer Institute] in Mexico, 193 new cases of plasma
cells myeloma were diagnosed between 2000-2004; of
these 92 were men and 101 were women, and repre-
sented 1% of all the neop lasms diagnosed at this Institute
[7].
At the General Hospital of Mexico, 21 patients were
diagnosed with plasma cells neoplasm in a 2-year period,
of which 12 were myelomas and 9 were plasmacytomas.
In the USA, plasma cells myeloma corresponds to 1% of
the total of all malignant tumors and to 10% to 15% of
the hematopoietic neoplasms [8,9]. Bone and extraosseous
plasmacytomas comprise 3% to 5% of plasmatic cell
neoplasms in the USA [10].
The etiology is still unknown; however, they have
been related with chronic antigenic stimulation due to
infection, or with the exposure to specific toxic sub st a n c es
or radiation [11]. Ries et al. observed that plasma cells
myeloma, bone and extraosseous plasmacytoma are more
common in men th an in women [9]. Accordin g to Rizo et
al. [7] from the Instituto Nacional de Cancerología, and
our results women predominate, as can be observed in
Tables 1 and 2. The ave rag e age fo r myel o mas was of 54
years, and 52 years for plasmacytomas. In the Western
literature the average age for myeloma patients is 70
years, and 55 years for plasmacytomas [1].
The clinical presentation of plasma cells myeloma
varies [12] and occasionally the symptomatic diagnosis is
delayed several months; the main bone symptoms are
lumbar pain or fractures of the affected bones. In the
present work, pain was the predominant symptom in
myeloma (Table 1), renal failure results from the tubu lar
damage caused by the proteinuria of the monoclonal light
chain proteins. One patient presented altered renal func-
tion and gammopathy, and in another it was not associ-
ated with gammopathy. Fractures were found in two pa-
tients. Among the altered laboratory tests, in the systemic
form of the disease, we found anemia, hypercalcemia
(>12 mg/dL), hyperviscocity, monoclonal peak as re-
vealed by protein electrophoresis, protein C reactive, and
elevation of LDH. Anemia was the most frequent altera-
tion found in both the study performed by Kyle in the
Mayo Clinic with 1027 patients (67% of patients with
anemia) and in this study with a similar percentage of
affectation (66.6%). The presence of anemia in patients
Table 2. Clinicopathological characteristics of extraosseus and osseus plasmacytomas.
Case Gender Age Site Morphology Inmunohistochemistry
1 m 49 gum/tumor MPC CD 138/Kappa
2 m 54 nasal/epistaxis MPC CD 138/Kappa CD 56
3 w 75 palate/tumor MPC CD 138/Lambda
4 w 63 nasal/epistaxis MPC CD 138/Kappa CD 56
5 m 84 antrochoanal/tumor MPC CD 138/Kappa
6 w 79 palate/lymphoplasmatic infiltration MPC CD 138/Lambda
7 w 57 sternun/tumor MPC CD 138/Kappa CD 56
8 w 57 SC MPC CD 138/Kappa CD 56
9 m 22 GL MPC CD 138/Lambda
MPC (mature plasmatic cells). No laboratory tests alterat io ns were observed in a ny patient. CD 20 and CD 5 were ne g ative in neoplastic plasma cells.

Plasma Cell Neoplasms, Clinicopathological Characteristics and Immunophenotype of 21 Patients 131
results first by the replacement of bone marrow by neo-
plastic plasma cells and/or because of renal damage re-
sulting from the loss of erythropoietin [13]. The other
laboratory alteration found in this series was the eleva-
tion of beta-2-micro globulin in serum, which is us ed as a
survival marker, if it is higher than 5.5 mg/dL, patient’s
survival is reduced to only 28 months; therefore, it is an
important prognostic laboratory marker [14].
Clinical variants of plasma cells myeloma include the
smoldering plasma cells myeloma, in which the patients
course with stable disease for long periods of time, it
presents with solitary plasmacytoma with bone ab nor ma l i -
ties detected only through Magnetic Resonance Image
(MRI) and only 10% - 20% of plasmatic cells are seen in
the bone marrow [1].
Another variant is the non-secreting myeloma that
corresponds to 3% of plasmatic cells myeloma. There is
lack of protein M as assessed through fixation el ectr oph o-
resis. [10] Leukemia of plasmatic cells is characterized
by an increase in the number of clonal plasmatic cells in
peripheral blood and exceeds 2 × 10/L, (2 × 109/L,) or
when the neoplastic plasma cells are encountered in ex-
tra-medullary sites, such as the spleen, liv er, pleural fluid,
ascites, and cerebrospinal fluid; it can associate second-
darily to a plasmatic cells myeloma during the course of
the disease, [1] we did not identify any such case in our
study. In 2006, 10 patien ts of the Institu to Naciona l de la
Nutrición y Ciencias Médicas [National Institute of Nu-
trition and Medical Sciences] were reported with a ful-
minant clinical condition, the average age of the patients
was 58 years and again women predom i na t e d [ 1 5 ].
By definition, extraosseous plas macytomas are located
in tissues outside the bone; in the present study, the most
affected site was the upper respiratory tract including the
oropharynx. The plasmacytoma in the lymph node oc-
curred adjacent to hyaline-vesicular type Castleman’s
disease. Bone plasmacytoma was found one in the spinal
cord and the other in the sternum. Histologically, the
mature plasma cells predominated in the myelomas, their
arrangement in the bone marrow is in groups interstitially,
and when the bone marrow is not completely substituted
normal hematopoietic elements can be observed; hence,
it is important to use markers such as CD 138 or CD 79a,
and light immunoglobulins to discard the disease. It is
important to consider the percentage of plasmatic cells in
the bone marrow that should be at least of 30%; another
observed change is osteoclastic activity [16].
Histologically, we observed an almost complete sub-
stitution of the normal bone marrow elements by abun-
dant plasmatic cells and CD 138 expression was almost
100%, expression for Kappa and Lambda light chains
was the same. CD 56 is expressed aberrantly en plasma
cells myeloma up to 70% [17]. In the pre sent r evie w, th is
marker was only expressed in two cases, one with a
morphology of mature plasmatic cells and the other with
immature p lasma cells.
Aside from CD 56 other markers have been expressed,
such as CD 117, CD 20, and CD 10; in contrast to plas-
matic cells myeloma, expression of CD 56 is negative in
plasmatic cells leukemia [18].
In plasmacytomas, mature morphology was observed
in seven patients, and two showed lymphoplasmacytic
morphology; expression of CD 56 was observed in four
cases, three with mature morphology and one with lym-
phoplasmacytic morphology.
Expression of CD 20 favors the diagnosis of infiltration
due to lymphoma, hence it must be taken into account for
the differential diagnosis. The immunophenotype of this
form of plasmatic cells neoplasm has not been studied
extensively, but apparently it is similar to the myeloma
phenotype. Expression of CD 56 was observed more
frequently in this form, however, more studies have to be
made, because probably this last marker could be used as
a prognostic marker in the future.
Although diverse genetic anomalies have been ob-
served through f luorescence in situ hybr idization (FISH),
such as in (13q14), hyperdiploidia, t (11; 14), among
others; however, the most frequent translocation in plas-
matic cells myeloma is the one affecting chromosome
14q23 with a 70% frequency [19]. It is noteworthy, that
patients with myeloma associated to translocation t (11;
14) (q13; q32) are usually positive to cyclin D-1 and are
associated with lymphoplasmacytic morphology with
extensive infiltration to the bone marrow. In this work,
only two cases presented this morphology and positivity
to cyclin D-1 in the cytoplasm o f the cells and not in the
nucleus [20,21]. In plasmacytomas, the expression of
Kappa and Lambda is very important to demonstrate
clonality and to confirm the diagnosis. There are reports
in the literature on the frequency of CD 56 expression
and the prognostic of the patients with myeloma, which,
as well known, is a marker of NK cells and of some T
cell subpopulations [22].
In conclusion, we observed that the myeloma and the
localized form, the extramedullary plasmacytoma, are the
most frequent. The average age of patients for the mye-
loma group was of 54.2 year in this series and, in patients
studied in two other national institutions, the age was
below 60 years, that is, 15 years younger than that re-
ported for American patients. Myeloma and another
plasma cell neoplasms are not found in children and is
rare in adults younger than 35 years. In our milieu,
women are more affected.
Morphologically, the presence of mature plasmatic
cells predominated in both types of disease, and CD 56
expression was observed in the localized form of the
disease.

Plasma Cell Neoplasms, Clinicopathological Characteristics and Immunophenotype of 21 Patients 132
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Abbreviations
WHO = World Health Organization.
MRI = Magnetic Resonance Imagen
B-2m = Beta-2 microglobulin
LDH = Lactic Dehydrogenase
ARF = Altered Renal Function
PBJ = Bence-Jones Protein
P
reg = Pregnancy
WG = Weeks of Gestation
MPC = Mature Plasma Cells
IPC = Immature Plasma Cells
PF = Pathological Fracture
VC = Vertebral Column
BM = Bone Marrow
LN = Lymph Node