Discussion:
This case illustrates an aggressive form of multiple myeloma that
presented with both plasmacytic ascites and pleural effusion in the late
stages of disease. The incidence of extra-medullary involvement in MM is
about 7%, and that of malignant effusions is 1-2% which is usually
associated with a poor prognosis. [9]
[10]
[11] Classic presenting symptoms and
signs of MM include anemia, bone pain, renal failure, infections, and
hypercalcemia. Effusions due to MM commonly occur due to secondary
involvement of other organs like heart and kidney. Malignant ascites can
occasionally be a presenting feature in MM, but myelomatous pleural
effusion rarely manifests at initial diagnosis.
[11]
[12]
[13] Four out of seven cases of MM with
a malignant effusion that were reported by Gochhaitt et al presented
with pleural effusion during their treatment with no other sites of
involvement. All the four MM cases were first recognized based on the
typical clinical presentation of hypercalcemia–renal
function–anemia–bone lesion (CRAB).
[10] Mitra et al reported case of an
elderly male who was evaluated for ascites with abdominal pain and
distension with high total protein but normal bilirubin and liver
enzymes. Computed tomography (CT) scan of the abdomen revealed multiple
peritoneal nodules, mesenteric and omental thickening. Both this and
another MM patient reported by Abdulsamad et al presented with ascites
at initial diagnosis unlike our patient who suffered from multiple
relapses over 7 to 8 years and ultimately developed extra-osseous
complications at an advanced stage of MM.
[7, 8]
The body cavities are not unusual sites of metastasis, but the
pathophysiology of their involvement is poorly understood. A pleural or
peritoneal biopsy may show extensive plasma cell infiltration, but it is
not necessary for diagnosis. [12]
[13] The diagnosis of plasmacytic
effusion can be confirmed based on detection of atypical plasma cells on
fluid cytological analysis derived via paracentesis and/or
thoracocentesis supplemented by immunofixation of proteins and
identification of cytoplasmic immunoglobin, kappa or lambda light
chains, and high CD38 and/or CD138 expression on their immunophenotypic
analysis. [12]
[14] An abdominal paracentesis in the
case reported by Mitra did not reveal any significant findings.
Histopathological examination of centrifuged peritoneal deposits showed
CD138 positive plasma cells on immunohistochemistry. Serum
electrophoresis confirmed the presence of IgG heavy chains and lambda
light chains that led to the diagnosis of MM, IgG lambda, ISS Stage III.
Similar findings were noted on flow cytometric immunophenotyping in the
four patients described by Gochhaitt et al.
[10] In one patient as described by
Stoos-Veic et al, a diagnosis of myelomatous ascites was confirmed by
flow cytometry immunophenotyping and presence of IgG kappa light chains
on ascitic fluid immuno-electrophoresis.
[15] Ghorbel et al described a case of
an adult female diagnosed with MM Stage IIIa based on a serum
electrophoresis, imaging, and bone marrow aspiration. Her clinical
presentation was typical with worsening bone pain and classic fatigue
but in about five months of treatment initiation, new respiratory
symptoms led to the diagnosis of myelomatous pleural effusion based on a
chest X-ray, thoracentesis, and a pleural biopsy.
[16]
To help rule out secondary causes of effusion in MM such as infections,
secondary tumors, renal or heart failure, ascitic fluid can be examined
to calculate the serum ascites albumin gradient (SAAG) ratio, pleural
fluid for pleural fluid/serum lactate dehydrogenase (LDH) ratio,
adenosine deaminase (ADA) and glucose levels, and both for cell counts
and cultures. [13]
[17] Imaging modalities like skeletal
survey, PET-CT scan and MRI are also commonly used to corroborate a
diagnosis of MM bone disease and extra-medullary MM.
[18] Alegre et al documented a disease
presentation of similar nature as our patient, i.e., development of
features of extramedullary MM in the form of ascites and pleural
effusion later in the disease course. After remaining asymptomatic with
a stage IA IgG multiple myeloma for 8 years after induction treatment,
she abruptly presented with moderate ascites, unexplained fever, and
pancytopenia due to bone marrow infiltration. A paracentesis
demonstrated 93% atypical plasma cells on fluid cytology and monoclonal
cytoplasmic kappa light chains on immunohistochemistry.
[19]
Finally, myelomatous effusions seems to predict poor outcomes with short
time to demise in the relapsed and refractory setting
[15]
[16]
[19]
[20]
[21] it is important to recognize this
entity as it might help differentiate infectious etiologies versus
disease relapses in MM patients.