ARTICLE
Plasmacytoma
is a localized collection of tumorous plasma cells.
Cutaneous plasmacytomas may occur in the absence of myeloma (primary cutaneous
plasmacytoma, PCP) or may appear during the course of multiple myeloma (secondary
plasmacytoma). While in multiple myeloma cutaneous plasmacytoma represents
5-10% of cases [1], only about 30 cases of PCP, mostly isolated cases, have
been documented in the literature since the first case was described in
1949 [2-5]. Due to its extreme rarity, PCP has been considered a "provisional
entity" among the B-cell lymphomas in the recent EORTC (European Organization
for Research and Treatment of Cancer) classification for primary cutaneous
lymphomas [6].
We report a further case of PCP with multiple cutaneous lesions arising
on chronic lymphoedema.
Case report
A 77-year-old patient was admitted for chronic lymphoedema of both his
lower limbs, leg ulcers and relapsing erysipela of his left leg.
Lymphoedema had started 40 years previously, after a lymphadenectomy
probably due to inflammatory suppurative adenitis; the lymphoedema had
reached the stage of elephantiasis involving the genitals and both legs.
On hospitalization, a few scattered asymptomatic papulo-nodular hemispheric
purplish-red lesions were found on his left thigh. Two weeks later they
had become larger and more numerous (Fig.
1).
A biopsy from a nodule showed a dense predominantly plasmacytic infiltration
of the reticular dermis extending into the subcutis; a "Grenz zone" under
the epidermis was noticed (Fig.
2). Plasma cells were frequently atypical, with basophilic cytoplasm,
prominent nucleoli and frequent mitosis (Fig.
3). No amyloid was found with the Congo red stain. Immunohistochemical
staining showed that plasma cells were monoclonal for lambda light chains
(Fig. 4).
No abnormalities were found in the complete blood cell count. Erythrocyte
sedimentation rate was very slightly increased (16 mm).
The search for Bence Jones protein was weakly positive for the presence
of free light monoclonal lambda chains; this data was interpreted as compatible
with the secretion from the plasma cells in the cutaneous lesions. Immunofixation
revealed the presence of lambda chains. Further investigations such as
chest and skull X-ray, abdominal ultrasonography and bone marrow biopsy
were normal. Total body bone scintigraphy did not reveal any area of abnormal
captation.
The diagnosis of primary cutaneous plasmacytoma was made. Due to the
bad local condition of the leg, local radiotherapy was not considered.
Therapy with 5 cycles of melphalan 10 mg/day for 4 days monthly and systemic
prednisone (75 mg/day for five days and then scalar doses) was started.
At a 2-year follow-up the lesions were healed and no signs of progression
were evident.
Discussion
PCP represents only 2-4% of extramedullary plasmacytomas (EMP), i.e.
the plasmacytomas without medullary involvement [7]; EMP, in fact, mostly
affects the upper respiratory tract (80% of the cases). The rarity and
the aspecific morphology of cutaneous plasmacytomas (asymptomatic solitary
or multiple red-bluish papules or nodules that may ulcerate and do not
show predilection of site) does not allow a clinical diagnosis. Only histopathology
reveals the typical pattern represented by a dense monomorphic dermal
plasmacytic infiltrate which is usually separated from the overlying epidermis
by a "Grenz zone". Immunohistochemical staining shows the typical monoclonality
of the neoplastic cells.
Neoplastic plasma cells are usually differentiated, with occasional
atypical features and mitotic figures. Nevertheless they may assume different
forms ranging from anaplastic large cells to signet ring cells which can
resemble metastatic carcinoma or neuroepithelioma. In the experience of
Torne et al. [8] the prognosis does not seem to be worse in the
presence of atypia and mitoses. Plasmacytoma must also be differentiated
from plasma cell infiltrates accompanying appendageal tumors such as syringocystadenoma,
from reactive granulomas such as syphilis or granuloma inguinale. Differential
diagnosis is mainly based on histopathologic features and demonstration
of monoclonality of neoplastic cells. Plasmacytoma should also be differentiated
from cutaneous immunocytoma/marginal zone lymphoma (MZL) with predominant
population of plasma cells. In plasmacytoma there is a nodular or diffuse
infiltrate consisting almost entirely of monoclonal plasma cells CD20
negative without mixture of neoplastic lymphocytes CD20 positive, a feature
which discriminates these lesions from MZL with prominent plasmacytic
differentiation.
For the diagnosis of PCP another criteria must be verified: the exclusion
of an underlying multiple myeloma [3].
The pathogenesis of PCP is unknown; the disease was described in a patient
with chronic lymphatic leukemia at the site of a previous herpes simplex
lesion and other cases were connected with herpes zoster, insect bites
or vaccine injections [8-10]. It has been suggested that these various
causes may induce a polyclonal reaction from which a clone of abnormal
plasma cells is selected [9]. In our patient chronic lymphoedema and recurrent
erysipelas may be hypothesized as factors which could promote this kind
of persistent immunological stimulation. Similarly it is well known that
chronic lymphoedema may favour the appearance of other neoplastic pathologies
like angiosarcoma of Stewart-Treves.
Another pathogenetic theory suggests that interleukin-6
(IL-6), a cytokine inducing B-cell differentiation to immunoglobulin producing
cells may have a role to play. Yamamoto et al. [11] found a high
level of IL-6 in patients with cutaneous plasmacytosis. Clinical improvement
was proportional to the reduction of levels of IL-6 as a result of a therapy
with intralesional steroids [11]. The authors suggested that an abnormal
production of IL-6 may give rise to a proliferation of plasma cells.
Surgical excision, radiation therapy and chemotherapy are all reported
as successful treatments. Intralesional injections of tumour necrosis
factor-alpha were also an effective treatment of multiple cutaneous plasmacytoma
[4].
The prognosis of PCP is still controversial [3, 12, 13]. Even if in
about 50% of cases PCP does not show an evolutive course (especially those
presenting as solitary lesions), local recurrences or progression of disease
towards a metastatic spread or multiple myeloma are often described within
one year from diagnosis. The presence of serum paraproteinemia seems not
to influence the prognosis [14].
As the disease-related mortality has been estimated as 40% [13], a close
follow up of patients with cutaneous plasmacytoma is mandatory.
Article accepted on 16/10/01
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